AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
PDF (1.1 MB)
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Review | Open Access

Cancer stem cells: a target for overcoming therapeutic resistance and relapse

Shuo Zhang1Rui Yang2Yujie Ouyang3Yang Shen4,5,6Lanlin Hu4,5,7,8 ( )Chuan Xu4,5,7,8 ( )
Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610042, China
Department of Ultrasound in Medicine, Chengdu Wenjiang District People’s Hospital, Chengdu 611130, China
Acupuncture and Massage College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
Department of Oncology & Cancer Institute, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China
Sichuan Provincial Key Laboratory for Human Disease Gene Study, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China
School of Pharmacy, Macau University of Science and Technology, Macau SAR 999078, China
Yu-Yue Pathology Scientific Research Center, Chongqing 400039, China
Jinfeng Laboratory, Chongqing 401329, China
Show Author Information

Abstract

Cancer stem cells (CSCs) are a small subset of cells in cancers that are thought to initiate tumorous transformation and promote metastasis, recurrence, and resistance to treatment. Growing evidence has revealed the existence of CSCs in various types of cancers and suggested that CSCs differentiate into diverse lineage cells that contribute to tumor progression. We may be able to overcome the limitations of cancer treatment with a comprehensive understanding of the biological features and mechanisms underlying therapeutic resistance in CSCs. This review provides an overview of the properties, biomarkers, and mechanisms of resistance shown by CSCs. Recent findings on metabolic features, especially fatty acid metabolism and ferroptosis in CSCs, are highlighted, along with promising targeting strategies. Targeting CSCs is a potential treatment plan to conquer cancer and prevent resistance and relapse in cancer treatment.

References

1

Mackillop WJ, Ciampi A, Till JE, Buick RN. A stem cell model of human tumor growth: implications for tumor cell clonogenic assays. J Natl Cancer Inst. 1983; 70: 9-16.

2

O’Brien CA, Kreso A, Dick JE. Cancer stem cells in solid tumors: an overview. Semin Radiat Oncol. 2009; 19: 71-7.

3

Vetrie D, Helgason GV, Copland M. The leukaemia stem cell: similarities, differences and clinical prospects in CML and AML. Nat Rev Cancer. 2020; 20: 158-73.

4

Zhang R, Tu J, Liu S. Novel molecular regulators of breast cancer stem cell plasticity and heterogeneity. Semin Cancer Biol. 2022; 82: 11-25.

5

Yu D, Liu Y, Yang J, Jin C, Zhao X, Cheng J, et al. Clinical implications of BMI-1 in cancer stem cells of laryngeal carcinoma. Cell Biochem Biophys. 2015; 71: 261-9.

6

Xu C, Jin G, Wu H, Cui W, Wang YH, Manne RK, et al. SIRPγ-expressing cancer stem-like cells promote immune escape of lung cancer via Hippo signaling. J Clin Invest. 2022; 132: e141797.

7

Ricci-Vitiani L, Pallini R, Biffoni M, Todaro M, Invernici G, Cenci T, et al. Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells. Nature. 2010; 468: 824-8.

8

Soda Y, Marumoto T, Friedmann-Morvinski D, Soda M, Liu F, Michiue H, et al. Transdifferentiation of glioblastoma cells into vascular endothelial cells. Proc Natl Acad Sci U S A. 2011; 108: 4274-80.

9

Cheng L, Huang Z, Zhou W, Wu Q, Donnola S, Liu JK, et al. Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth. Cell. 2013; 153: 139-52.

10

Kumon K, Afify SM, Hassan G, Ueno S, Monzur S, Nawara HM, et al. Differentiation of cancer stem cells into erythroblasts in the presence of CoCl(2). Sci Rep. 2021; 11: 23977.

11

Jiang G, Tu J, Zhou L, Dong M, Fan J, Chang Z, et al. Single-cell transcriptomics reveal the heterogeneity and dynamic of cancer stem-like cells during breast tumor progression. Cell Death Dis. 2021; 12: 979.

12

Zhou HM, Zhang JG, Zhang X, Li Q. Targeting cancer stem cells for reversing therapy resistance: mechanism, signaling, and prospective agents. Signal Transduct Target Ther. 2021; 6: 62.

13

Huang T, Song X, Xu D, Tiek D, Goenka A, Wu B, et al. Stem cell programs in cancer initiation, progression, and therapy resistance. Theranostics. 2020; 10: 8721-43.

14

Ju F, Atyah MM, Horstmann N, Gul S, Vago R, Bruns CJ, et al. Characteristics of the cancer stem cell niche and therapeutic strategies. Stem Cell Res Ther. 2022; 13: 233.

15

Beier CP, Kumar P, Meyer K, Leukel P, Bruttel V, Aschenbrenner I, et al. The cancer stem cell subtype determines immune infiltration of glioblastoma. Stem Cells Dev. 2012; 21: 2753-61.

16

Gangoso E, Southgate B, Bradley L, Rus S, Galvez-Cancino F, McGivern N, et al. Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion. Cell. 2021; 184: 2454-70.e2426.

17

Anderson NM, Simon MC. The tumor microenvironment. Curr Biol. 2020; 30: R921-5.

18

Chen P, Hsu WH, Han J, Xia Y, DePinho RA. Cancer stemness meets immunity: from mechanism to therapy. Cell Rep. 2021; 34: 108597.

19

Bayik D, Lathia JD. Cancer stem cell-immune cell crosstalk in tumour progression. Nat Rev Cancer. 2021; 21: 526-36.

20

Zhou H, Tan L, Liu B, Guan XY. Cancer stem cells: recent insights and therapies. Biochem Pharmacol. 2023; 209: 115441.

21

Wu B, Shi X, Jiang M, Liu H. Cross-talk between cancer stem cells and immune cells: potential therapeutic targets in the tumor immune microenvironment. Mol Cancer. 2023; 22: 38.

22

Ramgolam K, Lauriol J, Lalou C, Lauden L, Michel L, de la Grange P, et al. Melanoma spheroids grown under neural crest cell conditions are highly plastic migratory/invasive tumor cells endowed with immunomodulator function. PLoS One. 2011; 6: e18784.

23

Morrison BJ, Steel JC, Morris JC. Reduction of MHC-I expression limits T-lymphocyte-mediated killing of Cancer-initiating cells. BMC Cancer. 2018; 18: 469.

24

Di Tomaso T, Mazzoleni S, Wang E, Sovena G, Clavenna D, Franzin A, et al. Immunobiological characterization of cancer stem cells isolated from glioblastoma patients. Clin Cancer Res. 2010; 16: 800-13.

25

Chikamatsu K, Takahashi G, Sakakura K, Ferrone S, Masuyama K. Immunoregulatory properties of CD44+ cancer stem-like cells in squamous cell carcinoma of the head and neck. Head Neck. 2011; 33: 208-15.

26

Liao T, Kaufmann AM, Qian X, Sangvatanakul V, Chen C, Kube T, et al. Susceptibility to cytotoxic T cell lysis of cancer stem cells derived from cervical and head and neck tumor cell lines. J Cancer Res Clin Oncol. 2013; 139: 159-70.

27

Sultan M, Vidovic D, Paine AS, Huynh TT, Coyle KM, Thomas ML, et al. Epigenetic silencing of TAP1 in Aldefluor(+) breast cancer stem cells contributes to their enhanced immune evasion. Stem Cells. 2018; 36: 641-54.

28

Burr ML, Sparbier CE, Chan KL, Chan YC, Kersbergen A, Lam EYN, et al. An evolutionarily conserved function of polycomb silences the MHC class I antigen presentation pathway and enables immune evasion in cancer. Cancer Cell. 2019; 36: 385-401.e388.

29

Kim GR, Ha GH, Bae JH, Oh SO, Kim SH, Kang CD. Metastatic colon cancer cell populations contain more cancer stem-like cells with a higher susceptibility to natural killer cell-mediated lysis compared with primary colon cancer cells. Oncol Lett. 2015; 9: 1641-6.

30

Ames E, Canter RJ, Grossenbacher SK, Mac S, Chen M, Smith RC, et al. NK cells preferentially target tumor cells with a cancer stem cell phenotype. J Immunol. 2015; 195: 4010-9.

31

Dianat-Moghadam H, Mahari A, Heidarifard M, Parnianfard N, Pourmousavi-Kh L, Rahbarghazi R, et al. NK cells-directed therapies target circulating tumor cells and metastasis. Cancer Lett. 2021; 497: 41-53.

32

Avril T, Vauleon E, Hamlat A, Saikali S, Etcheverry A, Delmas C, et al. Human glioblastoma stem-like cells are more sensitive to allogeneic NK and T cell-mediated killing compared with serumcultured glioblastoma cells. Brain Pathol. 2012; 22: 159-74.

33

Oh SJ, Yang JI, Kim O, Ahn EJ, Kang WD, Lee JH, et al. Human U87 glioblastoma cells with stemness features display enhanced sensitivity to natural killer cell cytotoxicity through altered expression of NKG2D ligand. Cancer Cell Int. 2017; 17: 22.

34

Li G, Nikkhoi SK, Hatefi A. Stem cell-assisted enzyme/prodrug therapy makes drug-resistant ovarian cancer cells vulnerable to natural killer cells through upregulation of NKG2D ligands. Med Oncol. 2023; 40: 110.

35

Tallerico R, Todaro M, Di Franco S, Maccalli C, Garofalo C, Sottile R, et al. Human NK cells selective targeting of colon cancerinitiating cells: a role for natural cytotoxicity receptors and MHC class I molecules. J Immunol. 2013; 190: 2381-90.

36

Luna JI, Grossenbacher SK, Sturgill IR, Ames E, Judge SJ, Bouzid LA, et al. Bortezomib augments natural killer cell targeting of stemlike tumor cells. Cancers (Basel). 2019; 11: 85.

37

Weng J, Han X, Liu K, Yang J, Wei S, Zhang Y, et al. CD44 3′-Untranslated region functions as a competing endogenous RNA to enhance NK sensitivity of liver cancer stem cell by regulating ULBP2 expression. Int J Biol Sci. 2019; 15: 1664-75.

38

Mohme M, Riethdorf S, Pantel K. Circulating and disseminated tumour cells - mechanisms of immune surveillance and escape. Nat Rev Clin Oncol. 2017; 14: 155-67.

39

Paczulla AM, Rothfelder K, Raffel S, Konantz M, Steinbacher J, Wang H, et al. Absence of NKG2D ligands defines leukaemia stem cells and mediates their immune evasion. Nature. 2019; 572: 254-9.

40

Kimura Y, Tsunedomi R, Yoshimura K, Matsukuma S, Shindo Y, Matsui H, et al. Immune evasion of hepatoma cancer stem-like cells from natural killer cells. Ann Surg Oncol. 2022; 29: 7423-33.

41

Bernareggi D, Xie Q, Prager BC, Yun J, Cruz LS, Pham TV, et al. CHMP2A regulates tumor sensitivity to natural killer cell-mediated cytotoxicity. Nat Commun. 2022; 13: 1899.

42

Wang B, Wang Q, Wang Z, Jiang J, Yu SC, Ping YF, et al. Metastatic consequences of immune escape from NK cell cytotoxicity by human breast cancer stem cells. Cancer Res. 2014; 74: 5746-57.

43

Jin H, Kim HJ. NK cells lose their cytotoxicity function against cancer stem cell-rich radiotherapy-resistant breast cancer cell populations. Int J Mol Sci. 2021; 22: 9639.

44

Park DJ, Sung PS, Kim JH, Lee GW, Jang JW, Jung ES, et al. EpCAM-high liver cancer stem cells resist natural killer cellmediated cytotoxicity by upregulating CEACAM1. J Immunother Cancer. 2020; 8: e000301.

45

Wang C, Li Y, Jia L, Kim JK, Li J, Deng P, et al. CD276 expression enables squamous cell carcinoma stem cells to evade immune surveillance. Cell Stem Cell. 2021; 28: 1597-613.e1597.

46

Mansour FA, Al-Mazrou A, Al-Mohanna F, Al-Alwan M, Ghebeh H. PD-L1 is overexpressed on breast cancer stem cells through notch3/mTOR axis. Oncoimmunology. 2020; 9: 1729299.

47

Yin S, Guo Y, Wen X, Zeng H, Chen G. Increased expression of PD-L1 in endometrial cancer stem-like cells is regulated by hypoxia. Front Biosci (Landmark Ed). 2022; 27: 23.

48

Fu L, Fan J, Maity S, McFadden G, Shi Y, Kong W. PD-L1 interacts with Frizzled 6 to activate beta-catenin and form a positive feedback loop to promote cancer stem cell expansion. Oncogene. 2022; 41: 1100-13.

49

Koh YW, Han JH, Haam S. Expression of PD-L1, cancer stem cell and epithelial-mesenchymal transition phenotype in non-small cell lung cancer. Pathology. 2021; 53: 239-46.

50

Yamaguchi H, Hsu JM, Yang WH, Hung MC. Mechanisms regulating PD-L1 expression in cancers and associated opportunities for novel small-molecule therapeutics. Nat Rev Clin Oncol. 2022; 19: 287-305.

51

Hsu JM, Xia W, Hsu YH, Chan LC, Yu WH, Cha JH, et al. STT3-dependent PD-L1 accumulation on cancer stem cells promotes immune evasion. Nat Commun. 2018; 9: 1908.

52

Sun L, Wang Q, Chen B, Zhao Y, Shen B, Wang H, et al. Gastric cancer mesenchymal stem cells derived IL-8 induces PD-L1 expression in gastric cancer cells via STAT3/mTOR-c-Myc signal axis. Cell Death Dis. 2018; 9: 928.

53

Castagnoli L, Cancila V, Cordoba-Romero SL, Faraci S, Talarico G, Belmonte B, et al. WNT signaling modulates PD-L1 expression in the stem cell compartment of triple-negative breast cancer. Oncogene. 2019; 38: 4047-60.

54

Darvin P, Sasidharan Nair V, Elkord E. PD-L1 expression in human breast cancer stem cells is epigenetically regulated through posttranslational histone modifications. J Oncol. 2019; 2019: 3958908.

55

Perry JM, Tao F, Roy A, Lin T, He XC, Chen S, et al. Overcoming Wnt-β-catenin dependent anticancer therapy resistance in leukaemia stem cells. Nat Cell Biol. 2020; 22: 689-700.

56

Huang C, Chen B, Wang X, Xu J, Sun L, Wang D, et al. Gastric cancer mesenchymal stem cells via the CXCR2/HK2/PD-L1 pathway mediate immunosuppression. Gastric Cancer. 2023; 26: 691-707.

57

Hua F, Shang S, Yang YW, Zhang HZ, Xu TL, Yu JJ, et al. TRIB3 interacts with beta-catenin and TCF4 to increase stem cell features of colorectal cancer stem cells and tumorigenesis. Gastroenterology. 2019; 156: 708-21.e715.

58

Zhou S, Zhu J, Xu J, Gu B, Zhao Q, Luo C, et al. Anti-tumour potential of PD-L1/PD-1 post-translational modifications. Immunology. 2022; 167: 471-81.

59

Ma X, Wu J, Wang B, Liu C, Liu L, Sun C. Epigenetic modifications: critical participants of the PD-L1 regulatory mechanism in solid tumors (Review). Int J Oncol. 2022; 61: 134.

60

Kursunel MA, Taskiran EZ, Tavukcuoglu E, Yanik H, Demirag F, Karaosmanoglu B, et al. Small cell lung cancer stem cells display mesenchymal properties and exploit immune checkpoint pathways in activated cytotoxic T lymphocytes. Cancer Immunol Immunother. 2022; 71: 445-59.

61

Liu S, Zhang C, Wang B, Zhang H, Qin G, Li C, et al. Regulatory T cells promote glioma cell stemness through TGF-beta-NF-kappaBIL6-STAT3 signaling. Cancer Immunol Immunother. 2021; 70: 2601-16.

62

Liu X, Zhang Z, Zhao G. Recent advances in the study of regulatory T cells in gastric cancer. Int Immunopharmacol. 2019; 73: 560-7.

63

Qianmei Y, Zehong S, Guang W, Hui L, Lian G. Recent advances in the role of Th17/Treg cells in tumor immunity and tumor therapy. Immunol Res. 2021; 69: 398-414.

64

Rezalotfi A, Ahmadian E, Aazami H, Solgi G, Ebrahimi M. Gastric cancer stem cells effect on Th17/Treg balance; a bench to beside perspective. Front Oncol. 2019; 9: 226.

65

Madden EC, Gorman AM, Logue SE, Samali A. Tumour cell secretome in chemoresistance and tumour recurrence. Trends Cancer. 2020; 6: 489-505.

66

Larionova I, Cherdyntseva N, Liu T, Patysheva M, Rakina M, Kzhyshkowska J. Interaction of tumor-associated macrophages and cancer chemotherapy. Oncoimmunology. 2019; 8: 1596004.

67

Guo X, Zhao Y, Yan H, Yang Y, Shen S, Dai X, et al. Single tumorinitiating cells evade immune clearance by recruiting type Ⅱ macrophages. Genes Dev. 2017; 31: 247-59.

68

Wan S, Zhao E, Kryczek I, Vatan L, Sadovskaya A, Ludema G, et al. Tumor-associated macrophages produce interleukin 6 and signal via STAT3 to promote expansion of human hepatocellular carcinoma stem cells. Gastroenterology. 2014; 147: 1393-404.

69

Standiford TJ, Kunkel SL, Basha MA, Chensue SW, Lynch JP 3rd, Toews GB, et al. Interleukin-8 gene expression by a pulmonary epithelial cell line. A model for cytokine networks in the lung. J Clin Invest. 1990; 86: 1945-53.

70

Shimizu M, Tanaka N. IL-8-induced O-GlcNAc modification via GLUT3 and GFAT regulates cancer stem cell-like properties in colon and lung cancer cells. Oncogene. 2019; 38: 1520-33.

71

Huang R, Wang S, Wang N, Zheng Y, Zhou J, Yang B, et al. CCL5 derived from tumor-associated macrophages promotes prostate cancer stem cells and metastasis via activating β-catenin/STAT3 signaling. Cell Death Dis. 2020; 11: 234.

72

Jinushi M, Chiba S, Yoshiyama H, Masutomi K, Kinoshita I, Dosaka-Akita H, et al. Tumor-associated macrophages regulate tumorigenicity and anticancer drug responses of cancer stem/initiating cells. Proc Natl Acad Sci U S A. 2011; 108: 12425-30.

73

Cioffi M, Trabulo S, Hidalgo M, Costello E, Greenhalf W, Erkan M, et al. Inhibition of CD47 effectively targets pancreatic cancer stem cells via dual mechanisms. Clin Cancer Res. 2015; 21: 2325-37.

74

Xi Q, Zhang J, Yang G, Zhang L, Chen Y, Wang C, et al. Restoration of miR-340 controls pancreatic cancer cell CD47 expression to promote macrophage phagocytosis and enhance antitumor immunity. J Immunother Cancer. 2020; 8: e000253.

75

Tahk S, Vick B, Hiller B, Schmitt S, Marcinek A, Perini ED, et al. SIRPalpha-alphaCD123 fusion antibodies targeting CD123 in conjunction with CD47 blockade enhance the clearance of AMLinitiating cells. J Hematol Oncol. 2021; 14: 155.

76

Szczerba BM, Castro-Giner F, Vetter M, Krol I, Gkountela S, Landin J, et al. Neutrophils escort circulating tumour cells to enable cell cycle progression. Nature. 2019; 566: 553-7.

77

Aramini B, Masciale V, Arienti C, Dominici M, Stella F, Martinelli G, et al. Cancer stem cells (CSCs), circulating tumor cells (CTCs) and their interplay with cancer associated fibroblasts (CAFs): a new world of targets and treatments. Cancers (Basel). 2022; 14: 2408.

78

Ren Z, Chen Y, Shi L, Shao F, Sun Y, Ge J, et al. Sox9/CXCL5 axis facilitates tumour cell growth and invasion in hepatocellular carcinoma. FEBS J. 2022; 289: 3535-49.

79

Hwang WL, Lan HY, Cheng WC, Huang SC, Yang MH. Tumor stem-like cell-derived exosomal RNAs prime neutrophils for facilitating tumorigenesis of colon cancer. J Hematol Oncol. 2019; 12: 10.

80

Cui TX, Kryczek I, Zhao L, Zhao E, Kuick R, Roh MH, et al. Myeloid-derived suppressor cells enhance stemness of cancer cells by inducing microRNA101 and suppressing the corepressor CtBP2. Immunity. 2013; 39: 611-21.

81

Shidal C, Singh NP, Nagarkatti P, Nagarkatti M. MicroRNA-92 expression in CD133(+) melanoma stem cells regulates immunosuppression in the tumor microenvironment via integrindependent activation of TGFbeta. Cancer Res. 2019; 79: 3622-35.

82

Liu C, Qiang J, Deng Q, Xia J, Deng L, Zhou L, et al. ALDH1A1 activity in tumor-initiating cells remodels myeloid-derived suppressor cells to promote breast cancer progression. Cancer Res. 2021; 81: 5919-34.

83

Lee CG, Das B, Lin TL, Grimes C, Zhang X, Lavezzi T, et al. A rare fraction of drug-resistant follicular lymphoma cancer stem cells interacts with follicular dendritic cells to maintain tumourigenic potential. Br J Haematol. 2012; 158: 79-90.

84

Nelson A, Lukacs JD, Johnston B. The current landscape of NKT cell immunotherapy and the hills ahead. Cancers (Basel). 2021; 13: 5174.

85

Shen M, Sun Q, Wang J, Pan W, Ren X. Positive and negative functions of B lymphocytes in tumors. Oncotarget. 2016; 7: 55828-39.

86

Liao CP, Chen LY, Luethy A, Kim Y, Kani K, MacLeod AR, et al. Androgen receptor in cancer-associated fibroblasts influences stemness in cancer cells. Endocr Relat Cancer. 2017; 24: 157-70.

87

Burke CA. A statistical view of clinical trials in chronic hepatitis B. J Hepatol. 1986; 3 Suppl 2: S261-7.

88

Hasegawa T, Yashiro M, Nishii T, Matsuoka J, Fuyuhiro Y, Morisaki T, et al. Cancer-associated fibroblasts might sustain the stemness of scirrhous gastric cancer cells via transforming growth factor-β signaling. Int J Cancer. 2014; 134: 1785-95.

89

Lau EY, Lo J, Cheng BY, Ma MK, Lee JM, Ng JK, et al. Cancerassociated fibroblasts regulate tumor-initiating cell plasticity in hepatocellular carcinoma through c-Met/FRA1/HEY1 signaling. Cell Rep. 2016; 15: 1175-89.

90

Todaro M, Gaggianesi M, Catalano V, Benfante A, Iovino F, Biffoni M, et al. CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis. Cell Stem Cell. 2014; 14: 342-56.

91

Tsuyada A, Chow A, Wu J, Somlo G, Chu P, Loera S, et al. CCL2 mediates cross-talk between cancer cells and stromal fibroblasts that regulates breast cancer stem cells. Cancer Res. 2012; 72: 2768-79.

92

Huang M, Li Y, Zhang H, Nan F. Breast cancer stromal fibroblasts promote the generation of CD44+CD24- cells through SDF-1/CXCR4 interaction. J Exp Clin Cancer Res. 2010; 29: 80.

93

Wolfson B, Eades G, Zhou Q. Adipocyte activation of cancer stem cell signaling in breast cancer. World J Biol Chem. 2015; 6: 39-47.

94

Li H, Feng Z, He ML. Lipid metabolism alteration contributes to and maintains the properties of cancer stem cells. Theranostics. 2020; 10: 7053-69.

95

Mao J, Hu X, Xiao Y, Yang C, Ding Y, Hou N, et al. Overnutrition stimulates intestinal epithelium proliferation through β-catenin signaling in obese mice. Diabetes. 2013; 62: 3736-46.

96

Chen D, Liu S, Ma H, Liang X, Ma H, Yan X, et al. Paracrine factors from adipose-mesenchymal stem cells enhance metastatic capacity through Wnt signaling pathway in a colon cancer cell co-culture model. Cancer Cell Int. 2015; 15: 42.

97

Liu Z, Shi A, Song D, Han B, Zhang Z, Ma L, et al. Resistin confers resistance to doxorubicin-induced apoptosis in human breast cancer cells through autophagy induction. Am J Cancer Res. 2017; 7: 574-83.

98

Montrose DC, Galluzzi L. Drugging cancer metabolism: expectations vs. reality. Int Rev Cell Mol Biol. 2019; 347: 1-26.

99

Cipolleschi MG, Marzi I, Santini R, Fredducci D, Vinci MC, D’Amico M, et al. Hypoxia-resistant profile implies vulnerability of cancer stem cells to physiological agents, which suggests new therapeutic targets. Cell Cycle. 2014; 13: 268-78.

100

Aguilar E, Marin de Mas I, Zodda E, Marin S, Morrish F, Selivanov V, et al. metabolic reprogramming and dependencies associated with epithelial cancer stem cells independent of the epithelialmesenchymal transition program. Stem Cells. 2016; 34: 1163-76.

101

Chen EI, Hewel J, Krueger JS, Tiraby C, Weber MR, Kralli A, et al. Adaptation of energy metabolism in breast cancer brain metastases. Cancer Res. 2007; 67: 1472-86.

102

Sosa MS, Bragado P, Aguirre-Ghiso JA. Mechanisms of disseminated cancer cell dormancy: an awakening field. Nat Rev Cancer. 2014; 14: 611-22.

103

Emmink BL, Verheem A, Van Houdt WJ, Steller EJ, Govaert KM, Pham TV, et al. The secretome of colon cancer stem cells contains drug-metabolizing enzymes. J Proteomics. 2013; 91: 84-96.

104

Hammoudi N, Ahmed KB, Garcia-Prieto C, Huang P. Metabolic alterations in cancer cells and therapeutic implications. Chin J Cancer. 2011; 30: 508-25.

105

Peiris-Pagès M, Martinez-Outschoorn UE, Pestell RG, Sotgia F, Lisanti MP. Cancer stem cell metabolism. Breast Cancer Res. 2016; 18: 55.

106

Flavahan WA, Wu Q, Hitomi M, Rahim N, Kim Y, Sloan AE, et al. Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake. Nat Neurosci. 2013; 16: 1373-82.

107

Ciavardelli D, Rossi C, Barcaroli D, Volpe S, Consalvo A, Zucchelli M, et al. Breast cancer stem cells rely on fermentative glycolysis and are sensitive to 2-deoxyglucose treatment. Cell Death Dis. 2014; 5: e1336.

108

Liao J, Qian F, Tchabo N, Mhawech-Fauceglia P, Beck A, Qian Z, et al. Ovarian cancer spheroid cells with stem cell-like properties contribute to tumor generation, metastasis and chemotherapy resistance through hypoxia-resistant metabolism. PLoS One. 2014; 9: e84941.

109

Palorini R, Votta G, Balestrieri C, Monestiroli A, Olivieri S, Vento R, et al. Energy metabolism characterization of a novel cancer stem cell-like line 3AB-OS. J Cell Biochem. 2014; 115: 368-79.

110

Zhou Y, Zhou Y, Shingu T, Feng L, Chen Z, Ogasawara M, et al. Metabolic alterations in highly tumorigenic glioblastoma cells: preference for hypoxia and high dependency on glycolysis. J Biol Chem. 2011; 286: 32843-53.

111

Shen YA, Wang CY, Hsieh YT, Chen YJ, Wei YH. Metabolic reprogramming orchestrates cancer stem cell properties in nasopharyngeal carcinoma. Cell Cycle 2015; 14: 86-98.

112

Chen CL, Uthaya Kumar DB, Punj V, Xu J, Sher L, Tahara SM, et al. NANOG Metabolically reprograms tumor-initiating stem-like cells through tumorigenic changes in oxidative phosphorylation and fatty acid metabolism. Cell Metab. 2016; 23: 206-19.

113

Feng W, Gentles A, Nair RV, Huang M, Lin Y, Lee CY, et al. Targeting unique metabolic properties of breast tumor initiating cells. Stem Cells. 2014; 32: 1734-45.

114

Chen Z, He Q, Lu T, Wu J, Shi G, He L, et al. mcPGK1-dependent mitochondrial import of PGK1 promotes metabolic reprogramming and self-renewal of liver TICs. Nat Commun. 2023; 14: 1121.

115

Gu Y, Ji F, Liu N, Zhao Y, Wei X, Hu S, et al. Loss of miR-192-5p initiates a hyperglycolysis and stemness positive feedback in hepatocellular carcinoma. J Exp Clin Cancer Res. 2020; 39: 268.

116

Lee HJ, Li CF, Ruan D, He J, Montal ED, Lorenz S, et al. Nonproteolytic ubiquitination of Hexokinase 2 by HectH9 controls tumor metabolism and cancer stem cell expansion. Nat Commun. 2019; 10: 2625.

117

De Luca A, Fiorillo M, Peiris-Pagès M, Ozsvari B, Smith DL, Sanchez-Alvarez R, et al. Mitochondrial biogenesis is required for the anchorage-independent survival and propagation of stem-like cancer cells. Oncotarget. 2015; 6: 14777-95.

118

Janiszewska M, Suvà ML, Riggi N, Houtkooper RH, Auwerx J, Clément-Schatlo V, et al. Imp2 controls oxidative phosphorylation and is crucial for preserving glioblastoma cancer stem cells. Genes Dev. 2012; 26: 1926-44.

119

Lagadinou ED, Sach A, Callahan K, Rossi RM, Neering SJ, Minhajuddin M, et al. BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent human leukemia stem cells. Cell Stem Cell. 2013; 12: 329-41.

120

Lamb R, Bonuccelli G, Ozsvári B, Peiris-Pagès M, Fiorillo M, Smith DL, et al. Mitochondrial mass, a new metabolic biomarker for stem-like cancer cells: understanding WNT/FGF-driven anabolic signaling. Oncotarget. 2015; 6: 30453-71.

121

Pastò A, Bellio C, Pilotto G, Ciminale V, Silic-Benussi M, Guzzo G, et al. Cancer stem cells from epithelial ovarian cancer patients privilege oxidative phosphorylation, and resist glucose deprivation. Oncotarget. 2014; 5: 4305-19.

122

Sancho P, Burgos-Ramos E, Tavera A, Bou Kheir T, Jagust P, Schoenhals M, et al. MYC/PGC-1α balance determines the metabolic phenotype and plasticity of pancreatic cancer stem cells. Cell Metab. 2015; 22: 590-605.

123

Vlashi E, Lagadec C, Vergnes L, Reue K, Frohnen P, Chan M, et al. Metabolic differences in breast cancer stem cells and differentiated progeny. Breast Cancer Res Treat. 2014; 146: 525-34.

124

Lonardo E, Cioffi M, Sancho P, Sanchez-Ripoll Y, Trabulo SM, Dorado J, et al. Metformin targets the metabolic achilles heel of human pancreatic cancer stem cells. PLoS One. 2013; 8: e76518.

125

Farnie G, Sotgia F, Lisanti MP. High mitochondrial mass identifies a sub-population of stem-like cancer cells that are chemo-resistant. Oncotarget. 2015; 6: 30472-86.

126

Ye XQ, Li Q, Wang GH, Sun FF, Huang GJ, Bian XW, et al. Mitochondrial and energy metabolism-related properties as novel indicators of lung cancer stem cells. Int J Cancer. 2011; 129: 820-31.

127

Anderson AS, Roberts PC, Frisard MI, Hulver MW, Schmelz EM. Ovarian tumor-initiating cells display a flexible metabolism. Exp Cell Res. 2014; 328: 44-57.

128

Viale A, Pettazzoni P, Lyssiotis CA, Ying H, Sánchez N, Marchesini M, et al. Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature. 2014; 514: 628-32.

129

Ginestier C, Monville F, Wicinski J, Cabaud O, Cervera N, Josselin E, et al. Mevalonate metabolism regulates Basal breast cancer stem cells and is a potential therapeutic target. Stem Cells. 2012; 30: 1327-37.

130

Kim WY. Therapeutic targeting of lipid synthesis metabolism for selective elimination of cancer stem cells. Arch Pharm Res. 2019; 42: 25-39.

131

Dar S, Chhina J, Mert I, Chitale D, Buekers T, Kaur H, et al. Bioenergetic adaptations in chemoresistant ovarian cancer cells. Sci Rep. 2017; 7: 8760.

132

Pascual G, Avgustinova A, Mejetta S, Martín M, Castellanos A, Attolini CS, et al. Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature. 2017; 541: 41-5.

133

Tiong TY, Weng PW, Wang CH, Setiawan SA, Yadav VK, Pikatan NW, et al. Targeting the SREBP-1/Hsa-Mir-497/SCAP/FASN oncometabolic axis inhibits the cancer stem-like and chemoresistant phenotype of non-small cell lung carcinoma cells. Int J Mol Sci. 2022; 23: 7283.

134

Zheng J, Conrad M. The metabolic underpinnings of ferroptosis. Cell Metab. 2020; 32: 920-37.

135

Chen X, Kang R, Kroemer G, Tang D. Broadening horizons: the role of ferroptosis in cancer. Nat Rev Clin Oncol. 2021; 18: 280-96.

136

Taylor WR, Fedorka SR, Gad I, Shah R, Alqahtani HD, Koranne R, et al. Small-molecule ferroptotic agents with potential to selectively target cancer stem cells. Sci Rep. 2019; 9: 5926.

137

Turcu AL, Versini A, Khene N, Gaillet C, Caneque T, Muller S, et al. DMT1 inhibitors kill cancer stem cells by blocking lysosomal iron translocation. Chemistry. 2020; 26: 7369-73.

138

Basuli D, Tesfay L, Deng Z, Paul B, Yamamoto Y, Ning G, et al. Iron addiction: a novel therapeutic target in ovarian cancer. Oncogene. 2017; 36: 4089-99.

139

Mai TT, Hamai A, Hienzsch A, Caneque T, Muller S, Wicinski J, et al. Salinomycin kills cancer stem cells by sequestering iron in lysosomes. Nat Chem. 2017; 9: 1025-33.

140

Han M, Xu R, Wang S, Yang N, Ni S, Zhang Q, et al. Sixtransmembrane epithelial antigen of prostate 3 predicts poor prognosis and promotes glioblastoma growth and invasion. Neoplasia. 2018; 20: 543-54.

141

Song Q, Peng S, Sun Z, Heng X, Zhu X. Temozolomide drives ferroptosis via a DMT1-dependent pathway in glioblastoma cells. Yonsei Med J. 2021; 62: 843-9.

142

Lei G, Zhuang L, Gan B. Targeting ferroptosis as a vulnerability in cancer. Nat Rev Cancer. 2022; 22: 381-96.

143

Zhao B, Yu T, Wang S, Che J, Zhou L, Shang P. Static magnetic field (0.2-0.4 T) stimulates the self-renewal ability of osteosarcoma stem cells through autophagic degradation of ferritin. Bioelectromagnetics. 2021; 42: 371-83.

144

Liu CC, Li HH, Lin JH, Chiang MC, Hsu TW, Li AF, et al. Esophageal cancer stem-like cells resist ferroptosis-induced cell death by active Hsp27-GPX4 pathway. Biomolecules. 2021; 12: 48.

145

Chirillo R, Aversa I, Di Vito A, Salatino A, Battaglia AM, Sacco A, et al. FtH-mediated ROS dysregulation promotes CXCL12/CXCR4 axis activation and EMT-like trans-differentiation in erythroleukemia K562 cells. Front Oncol. 2020; 10: 698.

146

Zhang KH, Tian HY, Gao X, Lei WW, Hu Y, Wang DM, et al. Ferritin heavy chain-mediated iron homeostasis and subsequent increased reactive oxygen species production are essential for epithelial-mesenchymal transition. Cancer Res. 2009; 69: 5340-8.

147

Aversa I, Zolea F, Ierano C, Bulotta S, Trotta AM, Faniello MC, et al. Epithelial-to-mesenchymal transition in FHC-silenced cells: the role of CXCR4/CXCL12 axis. J Exp Clin Cancer Res. 2017; 36: 104.

148

Lobello N, Biamonte F, Pisanu ME, Faniello MC, Jakopin Z, Chiarella E, et al. Ferritin heavy chain is a negative regulator of ovarian cancer stem cell expansion and epithelial to mesenchymal transition. Oncotarget. 2016; 7: 62019-33.

149

Zhang H, Wang M, He Y, Deng T, Liu R, Wang W, et al. Chemotoxicity-induced exosomal lncFERO regulates ferroptosis and stemness in gastric cancer stem cells. Cell Death Dis. 2021; 12: 1116.

150

Li D, Fu Z, Chen R, Zhao X, Zhou Y, Zeng B, et al. Inhibition of glutamine metabolism counteracts pancreatic cancer stem cell features and sensitizes cells to radiotherapy. Oncotarget. 2015; 6: 31151-63.

151

Wu Z, Wei D, Gao W, Xu Y, Hu Z, Ma Z, et al. TPO-induced metabolic reprogramming drives liver metastasis of colorectal cancer CD110+ tumor-initiating cells. Cell Stem Cell. 2015; 17: 47-59.

152

Eramo A, Lotti F, Sette G, Pilozzi E, Biffoni M, Di Virgilio A, et al. Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ. 2008; 15: 504-14.

153

Tirino V, Camerlingo R, Franco R, Malanga D, La Rocca A, Viglietto G, et al. The role of CD133 in the identification and characterisation of tumour-initiating cells in non-small-cell lung cancer. Eur J Cardiothorac Surg. 2009; 36: 446-53.

154

Bertolini G, Roz L, Perego P, Tortoreto M, Fontanella E, Gatti L, et al. Highly tumorigenic lung cancer CD133+ cells display stemlike features and are spared by cisplatin treatment. Proc Natl Acad Sci U S A. 2009; 106: 16281-6.

155

O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007; 445: 106-10.

156

Vermeulen L, Todaro M, de Sousa Mello F, Sprick MR, Kemper K, Perez Alea M, et al. Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity. Proc Natl Acad Sci U S A. 2008; 105: 13427-32.

157

Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005; 65: 10946-51.

158

Kryczek I, Liu S, Roh M, Vatan L, Szeliga W, Wei S, et al. Expression of aldehyde dehydrogenase and CD133 defines ovarian cancer stem cells. Int J Cancer. 2012; 130: 29-39.

159

Grasso C, Anaka M, Hofmann O, Sompallae R, Broadley K, Hide W, et al. Iterative sorting reveals CD133+ and CD133- melanoma cells as phenotypically distinct populations. BMC Cancer. 2016; 16: 726.

160

Tirino V, Desiderio V, Paino F, De Rosa A, Papaccio F, Fazioli F, et al. Human primary bone sarcomas contain CD133+ cancer stem cells displaying high tumorigenicity in vivo. FASEB J 2011; 25: 2022-30.

161

Fujiwara T, Katsuda T, Hagiwara K, Kosaka N, Yoshioka Y, Takahashi RU, et al. Clinical relevance and therapeutic significance of microRNA-133a expression profiles and functions in malignant osteosarcoma-initiating cells. Stem Cells. 2014; 32: 959-73.

162

Cox CV, Diamanti P, Evely RS, Kearns PR, Blair A. Expression of CD133 on leukemia-initiating cells in childhood ALL. Blood. 2009; 113: 3287-96.

163

Suetsugu A, Nagaki M, Aoki H, Motohashi T, Kunisada T, Moriwaki H. Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem Biophys Res Commun. 2006; 351: 820-4.

164

Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, et al. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell. 2007; 1: 313-23.

165

Ma Z, Zhang C, Liu X, Fang F, Liu S, Liao X, et al. Characterisation of a subpopulation of CD133(+) cancer stem cells from Chinese patients with oral squamous cell carcinoma. Sci Rep. 2020; 10: 8875.

166

Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A. 2007; 104: 10158-63.

167

Du L, Wang H, He L, Zhang J, Ni B, Wang X, et al. CD44 is of functional importance for colorectal cancer stem cells. Clin Cancer Res. 2008; 14: 6751-60.

168

Abbasian M, Mousavi E, Arab-Bafrani Z, Sahebkar A. The most reliable surface marker for the identification of colorectal cancer stem-like cells: a systematic review and meta-analysis. J Cell Physiol. 2019; 234: 8192-202.

169

Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, et al. Identification of pancreatic cancer stem cells. Cancer Res. 2007; 67: 1030-7.

170

Zhang S, Balch C, Chan MW, Lai HC, Matei D, Schilder JM, et al. Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res. 2008; 68: 4311-20.

171

Takaishi S, Okumura T, Tu S, Wang SS, Shibata W, Vigneshwaran R, et al. Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells. 2009; 27: 1006-20.

172

Chen W, Zhang X, Chu C, Cheung WL, Ng L, Lam S, et al. Identification of CD44+ cancer stem cells in human gastric cancer. Hepatogastroenterology. 2013; 60: 949-54.

173

Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S, et al. Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene. 2006; 25: 1696-708.

174

Leung EL, Fiscus RR, Tung JW, Tin VP, Cheng LC, Sihoe AD, et al. Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties. PLoS One. 2010; 5: e14062.

175

Patil S, Al-Brakati A, Abidi NH, Almasri MA, Almeslet AS, Patil VR, et al. CD44-positive cancer stem cells from oral squamous cell carcinoma exhibit reduced proliferation and stemness gene expression upon adipogenic induction. Med Oncol. 2022; 39: 23.

176

Hoe SLL, Tan LP, Abdul Aziz N, Liew K, Teow SY, Abdul Razak FR, et al. CD24, CD44 and EpCAM enrich for tumour-initiating cells in a newly established patient-derived xenograft of nasopharyngeal carcinoma. Sci Rep. 2017; 7: 12372.

177

Haraguchi N, Ohkuma M, Sakashita H, Matsuzaki S, Tanaka F, Mimori K, et al. CD133+CD44+ population efficiently enriches colon cancer initiating cells. Ann Surg Oncol. 2008; 15: 2927-33.

178

Zhu Z, Hao X, Yan M, Yao M, Ge C, Gu J, et al. Cancer stem/progenitor cells are highly enriched in CD133+CD44+ population in hepatocellular carcinoma. Int J Cancer. 2010; 126: 2067-78.

179

Cho RW, Wang X, Diehn M, Shedden K, Chen GY, Sherlock G, et al. Isolation and molecular characterization of cancer stem cells in MMTV-Wnt-1 murine breast tumors. Stem Cells. 2008; 26: 364-71.

180

Yang ZF, Ho DW, Ng MN, Lau CK, Yu WC, Ngai P, et al. Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell. 2008; 13: 153-66.

181

Jiang J, Zhang Y, Chuai S, Wang Z, Zheng D, Xu F, et al. Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 phenotype. Oncogene. 2012; 31: 671-82.

182

Tang KH, Dai YD, Tong M, Chan YP, Kwan PS, Fu L, et al. A CD90(+) tumor-initiating cell population with an aggressive signature and metastatic capacity in esophageal cancer. Cancer Res. 2013; 73: 2322-32.

183

Yan X, Luo H, Zhou X, Zhu B, Wang Y, Bian X. Identification of CD90 as a marker for lung cancer stem cells in A549 and H446 cell lines. Oncol Rep. 2013; 30: 2733-40.

184

Shi J, Lu P, Shen W, He R, Yang MW, Fang Y, et al. CD90 highly expressed population harbors a stemness signature and creates an immunosuppressive niche in pancreatic cancer. Cancer Lett. 2019; 453: 158-69.

185

He J, Liu Y, Zhu T, Zhu J, Dimeco F, Vescovi AL, et al. CD90 is identified as a candidate marker for cancer stem cells in primary high-grade gliomas using tissue microarrays. Mol Cell Proteomics. 2012; 11: M111.010744.

186

Parry PV, Engh JA. CD90 is identified as a marker for cancer stem cells in high-grade gliomas using tissue microarrays. Neurosurgery. 2012; 70: N23-4.

187

Buishand FO, Arkesteijn GJ, Feenstra LR, Oorsprong CW, Mestemaker M, Starke A, et al. Identification of CD90 as putative cancer stem cell marker and therapeutic target in insulinomas. Stem Cells Dev. 2016; 25: 826-35.

188

Yamashita T, Honda M, Nakamoto Y, Baba M, Nio K, Hara Y, et al. Discrete nature of EpCAM+ and CD90+ cancer stem cells in human hepatocellular carcinoma. Hepatology. 2013; 57: 1484-97.

189

Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003; 100: 3983-8.

190

Mal A, Bukhari AB, Singh RK, Kapoor A, Barai A, Deshpande I, et al. EpCAM-mediated cellular plasticity promotes radiation resistance and metastasis in breast cancer. Front Cell Dev Biol. 2020; 8: 597673.

191

Tsui YM, Chan LK, Ng IO. Cancer stemness in hepatocellular carcinoma: mechanisms and translational potential. Br J Cancer. 2020; 122: 1428-40.

192

Fong D, Steurer M, Obrist P, Barbieri V, Margreiter R, Amberger A, et al. Ep-CAM expression in pancreatic and ampullary carcinomas: frequency and prognostic relevance. J Clin Pathol. 2008; 61: 31-5.

193

Hu F, Sun X, Li G, Wu Q, Chen Y, Yang X, et al. Inhibition of SIRT2 limits tumour angiogenesis via inactivation of the STAT3/VEGFA signalling pathway. Cell Death Dis. 2018; 10: 9.

194

Wang K, Yuen ST, Xu J, Lee SP, Yan HH, Shi ST, et al. Wholegenome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat Genet. 2014; 46: 573-82.

195

Wang B, Chen Q, Cao Y, Ma X, Yin C, Jia Y, et al. LGR5 is a gastric cancer stem cell marker associated with stemness and the EMT signature genes NANOG, NANOGP8, PRRX1, TWIST1, and BMI1. PLoS One. 2016; 11: e0168904.

196

Jiang X, Hao HX, Growney JD, Woolfenden S, Bottiglio C, Ng N, et al. Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma. Proc Natl Acad Sci U S A. 2013; 110: 12649-54.

197

Mizuno N, Yatabe Y, Hara K, Hijioka S, Imaoka H, Shimizu Y, et al. Cytoplasmic expression of LGR5 in pancreatic adenocarcinoma. Front Physiol. 2013; 4: 269.

198

Cao W, Li M, Liu J, Zhang S, Noordam L, Verstegen MMA, et al. LGR5 marks targetable tumor-initiating cells in mouse liver cancer. Nat Commun. 2020; 11: 1961.

199

Akbari S, Kunter I, Azbazdar Y, Ozhan G, Atabey N, Firtina Karagonlar Z, et al. LGR5/R-Spo1/Wnt3a axis promotes stemness and aggressive phenotype in hepatoblast-like hepatocellular carcinoma cell lines. Cell Signal. 2021; 82: 109972.

200

Kemper K, Prasetyanti PR, De Lau W, Rodermond H, Clevers H, Medema JP. Monoclonal antibodies against Lgr5 identify human colorectal cancer stem cells. Stem Cells. 2012; 30: 2378-86.

201

Hirsch D, Barker N, McNeil N, Hu Y, Camps J, McKinnon K, et al. LGR5 positivity defines stem-like cells in colorectal cancer. Carcinogenesis. 2014; 35: 849-58.

202

Schindler AJ, Watanabe A, Howell SB. LGR5 and LGR6 in stem cell biology and ovarian cancer. Oncotarget. 2018; 9: 1346-55.

203

Cao HZ, Liu XF, Yang WT, Chen Q, Zheng PS. LGR5 promotes cancer stem cell traits and chemoresistance in cervical cancer. Cell Death Dis. 2017; 8: e3039.

204

Yang L, Tang H, Kong Y, Xie X, Chen J, Song C, et al. LGR5 promotes breast cancer progression and maintains stem-like cells through activation of Wnt/β-catenin signaling. Stem Cells. 2015; 33: 2913-24.

205

Du Z, Jia D, Liu S, Wang F, Li G, Zhang Y, et al. Oct4 is expressed in human gliomas and promotes colony formation in glioma cells. Glia. 2009; 57: 724-33.

206

Gzil A, Zarębska I, Bursiewicz W, Antosik P, Grzanka D, Szylberg Ł. Markers of pancreatic cancer stem cells and their clinical and therapeutic implications. Mol Biol Rep. 2019; 46: 6629-45.

207

Wang G, Zhou H, Gu Z, Gao Q, Shen G. Oct4 promotes cancer cell proliferation and migration and leads to poor prognosis associated with the survivin/STAT3 pathway in hepatocellular carcinoma. Oncol Rep. 2018; 40: 979-87.

208

Wu G, Wilson G, Zhou G, Hebbard L, George J, Qiao L. Oct4 is a reliable marker of liver tumor propagating cells in hepatocellular carcinoma. Discov Med. 2015; 20: 219-29.

209

Vaddi PK, Stamnes MA, Cao H, Chen S. Elimination of SOX2/OCT4-associated prostate cancer stem cells blocks tumor development and enhances therapeutic response. Cancers (Basel). 2019; 11: 1331.

210

Miyazawa K, Tanaka T, Nakai D, Morita N, Suzuki K. Immunohistochemical expression of four different stem cell markers in prostate cancer: high expression of NANOG in conjunction with hypoxia-inducible factor-1α expression is involved in prostate epithelial malignancy. Oncol Lett. 2014; 8: 985-92.

211

Hatefi N, Nouraee N, Parvin M, Ziaee SA, Mowla SJ. Evaluating the expression of oct4 as a prognostic tumor marker in bladder cancer. Iran J Basic Med Sci. 2012; 15: 1154-61.

212

Ruan Z, Yang X, Cheng W. OCT4 accelerates tumorigenesis through activating JAK/STAT signaling in ovarian cancer side population cells. Cancer Manag Res. 2019; 11: 389-99.

213

Lu CS, Shiau AL, Su BH, Hsu TS, Wang CT, Su YC, et al. Oct4 promotes M2 macrophage polarization through upregulation of macrophage colony-stimulating factor in lung cancer. J Hematol Oncol. 2020; 13: 62.

214

Lee SH, Oh SY, Do SI, Lee HJ, Kang HJ, Rho YS, et al. SOX2 regulates self-renewal and tumorigenicity of stem-like cells of head and neck squamous cell carcinoma. Br J Cancer. 2014; 111: 2122-30.

215

Cox JL, Wilder PJ, Desler M, Rizzino A. Elevating SOX2 levels deleteriously affects the growth of medulloblastoma and glioblastoma cells. PLoS One. 2012; 7: e44087.

216

Jeon HM, Sohn YW, Oh SY, Kim SH, Beck S, Kim S, et al. ID4 imparts chemoresistance and cancer stemness to glioma cells by derepressing miR-9*-mediated suppression of SOX2. Cancer Res. 2011; 71: 3410-21.

217

Lengerke C, Fehm T, Kurth R, Neubauer H, Scheble V, Müller F, et al. Expression of the embryonic stem cell marker SOX2 in earlystage breast carcinoma. BMC Cancer. 2011; 11: 42.

218

Tian T, Zhang Y, Wang S, Zhou J, Xu S. Sox2 enhances the tumorigenicity and chemoresistance of cancer stem-like cells derived from gastric cancer. J Biomed Res. 2012; 26: 336-45.

219

Fang X, Yu W, Li L, Shao J, Zhao N, Chen Q, et al. ChIP-seq and functional analysis of the SOX2 gene in colorectal cancers. Omics. 2010; 14: 369-84.

220

Hussenet T, Dali S, Exinger J, Monga B, Jost B, Dembelé D, et al. SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas. PLoS One. 2010; 5: e8960.

221

Liu XF, Yang WT, Xu R, Liu JT, Zheng PS. Cervical cancer cells with positive Sox2 expression exhibit the properties of cancer stem cells. PLoS One. 2014; 9: e87092.

222

Santini R, Pietrobono S, Pandolfi S, Montagnani V, D’Amico M, Penachioni JY, et al. SOX2 regulates self-renewal and tumorigenicity of human melanoma-initiating cells. Oncogene. 2014; 33: 4697-708.

223

Basu-Roy U, Seo E, Ramanathapuram L, Rapp TB, Perry JA, Orkin SH, et al. Sox2 maintains self renewal of tumor-initiating cells in osteosarcomas. Oncogene. 2012; 31: 2270-82.

224

Bareiss PM, Paczulla A, Wang H, Schairer R, Wiehr S, Kohlhofer U, et al. SOX2 expression associates with stem cell state in human ovarian carcinoma. Cancer Res. 2013; 73: 5544-55.

225

Herreros-Villanueva M, Zhang JS, Koenig A, Abel EV, Smyrk TC, Bamlet WR, et al. SOX2 promotes dedifferentiation and imparts stem cell-like features to pancreatic cancer cells. Oncogenesis. 2013; 2: e61.

226

Zhu F, Qian W, Zhang H, Liang Y, Wu M, Zhang Y, et al. SOX2 is a marker for stem-like tumor cells in bladder cancer. Stem Cell Rep. 2017; 9: 429-37.

227

Boumahdi S, Driessens G, Lapouge G, Rorive S, Nassar D, Le Mercier M, et al. SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma. Nature. 2014; 511: 246-50.

228

Yasunaga J, Taniguchi Y, Nosaka K, Yoshida M, Satou Y, Sakai T, et al. Identification of aberrantly methylated genes in association with adult T-cell leukemia. Cancer Res. 2004; 64: 6002-9.

229

Tang H, Zhu H, Wang X, Hua L, Li J, Xie Q, et al. KLF4 is a tumor suppressor in anaplastic meningioma stem-like cells and human meningiomas. J Mol Cell Biol. 2017; 9: 315-24.

230

Leng Z, Li Y, Zhou G, Lv X, Ai W, Li J, et al. Krüppel-like factor 4 regulates stemness and mesenchymal properties of colorectal cancer stem cells through the TGF-β1/Smad/snail pathway. J Cell Mol Med. 2020; 24: 1866-77.

231

Cho YG, Song JH, Kim CJ, Nam SW, Yoo NJ, Lee JY, et al. Genetic and epigenetic analysis of the KLF4 gene in gastric cancer. APMIS. 2007; 115: 802-8.

232

Bianchi F, Hu J, Pelosi G, Cirincione R, Ferguson M, Ratcliffe C, et al. Lung cancers detected by screening with spiral computed tomography have a malignant phenotype when analyzed by cDNA microarray. Clin Cancer Res. 2004; 10: 6023-8.

233

Li Q, Gao Y, Jia Z, Mishra L, Guo K, Li Z, et al. Dysregulated Krüppel-like factor 4 and vitamin D receptor signaling contribute to progression of hepatocellular carcinoma. Gastroenterology. 2012; 143: 799-810.e792.

234

Ohnishi S, Ohnami S, Laub F, Aoki K, Suzuki K, Kanai Y, et al. Downregulation and growth inhibitory effect of epithelial-type Krüppel-like transcription factor KLF4, but not KLF5, in bladder cancer. Biochem Biophys Res Commun. 2003; 308: 251-56.

235

Luo A, Kong J, Hu G, Liew CC, Xiong M, Wang X, et al. Discovery of Ca2+-relevant and differentiation-associated genes downregulated in esophageal squamous cell carcinoma using cDNA microarray. Oncogene. 2004; 23: 1291-9.

236

Zbinden M, Duquet A, Lorente-Trigos A, Ngwabyt SN, Borges I, Ruiz i Altaba A. NANOG regulates glioma stem cells and is essential in vivo acting in a cross-functional network with GLI1 and p53. EMBO J. 2010; 29: 2659-74.

237

Cao J, Li L, Chen C, Lv C, Meng F, Zeng L, et al. RNA interferencemediated silencing of NANOG leads to reduced proliferation and self-renewal, cell cycle arrest and apoptosis in T-cell acute lymphoblastic leukemia cells via the p53 signaling pathway. Leuk Res. 2013; 37: 1170-7.

238

Chiou SH, Wang ML, Chou YT, Chen CJ, Hong CF, Hsieh WJ, et al. Coexpression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation. Cancer Res. 2010; 70: 10433-44.

239

Bourguignon LY, Spevak CC, Wong G, Xia W, Gilad E. Hyaluronan-CD44 interaction with protein kinase C(epsilon) promotes oncogenic signaling by the stem cell marker Nanog and the Production of microRNA-21, leading to down-regulation of the tumor suppressor protein PDCD4, anti-apoptosis, and chemotherapy resistance in breast tumor cells. J Biol Chem. 2009; 284: 26533-46.

240

Narusaka T, Ohara T, Noma K, Nishiwaki N, Katsura Y, Kato T, et al. Nanog is a promising chemoresistant stemness marker and therapeutic target by iron chelators for esophageal cancer. Int J Cancer. 2021; 149: 347-57.

241

Ma X, Wang B, Wang X, Luo Y, Fan W. NANOGP8 is the key regulator of stemness, EMT, Wnt pathway, chemoresistance, and other malignant phenotypes in gastric cancer cells. PLoS One. 2018; 13: e0192436.

242

Tamura S, Isobe T, Ariyama H, Nakano M, Kikushige Y, Takaishi S, et al. E-cadherin regulates proliferation of colorectal cancer stem cells through NANOG. Oncol Rep. 2018; 40: 693-703.

243

Siu MK, Wong ES, Kong DS, Chan HY, Jiang L, Wong OG, et al. Stem cell transcription factor NANOG controls cell migration and invasion via dysregulation of E-cadherin and FoxJ1 and contributes to adverse clinical outcome in ovarian cancers. Oncogene. 2013; 32: 3500-9.

244

Jeter CR, Liu B, Lu Y, Chao HP, Zhang D, Liu X, et al. NANOG reprograms prostate cancer cells to castration resistance via dynamically repressing and engaging the AR/FOXA1 signaling axis. Cell Discov. 2016; 2: 16041.

245

Shan J, Shen J, Liu L, Xia F, Xu C, Duan G, et al. Nanog regulates self-renewal of cancer stem cells through the insulin-like growth factor pathway in human hepatocellular carcinoma. Hepatology. 2012; 56: 1004-14.

246

Bourguignon LY, Wong G, Earle C, Chen L. Hyaluronan-CD44v3 interaction with Oct4-Sox2-Nanog promotes miR-302 expression leading to self-renewal, clonal formation, and cisplatin resistance in cancer stem cells from head and neck squamous cell carcinoma. J Biol Chem. 2012; 287: 32800-24.

247

Zhang T, Sun H, Liu R, Cao W, Zhang T, Li E, et al. Nanog mediates tobacco smoke-induced enhancement of renal cancer stem cell properties. Environ Toxicol. 2020; 35: 1274-83.

248

Le Grand M, Mukha A, Püschel J, Valli E, Kamili A, Vittorio O, et al. Interplay between MycN and c-Myc regulates radioresistance and cancer stem cell phenotype in neuroblastoma upon glutamine deprivation. Theranostics. 2020; 10: 6411-29.

249

Hongwiangchan N, Sriratanasak N, Wichadakul D, Aksorn N, Chamni S, Chanvorachote P. Hydroquinone 5-O-cinnamoyl ester of renieramycin M suppresses lung cancer stem cells by targeting Akt and destabilizes c-Myc. Pharmaceuticals (Basel). 2021; 14: 1112.

250

Zhu Y, Wang C, Becker SA, Hurst K, Nogueira LM, Findlay VJ, et al. miR-145 antagonizes SNAI1-mediated stemness and radiation resistance in colorectal cancer. Mol Ther. 2018; 26: 744-54.

251

Choi HS, Kim SL, Kim JH, Deng HY, Yun BS, Lee DS. Triterpene acid (3-O-p-coumaroyltormentic acid) isolated from aronia extracts inhibits breast cancer stem cell formation through downregulation of c-Myc protein. Int J Mol Sci. 2018; 19: 2528.

252

Condello S, Morgan CA, Nagdas S, Cao L, Turek J, Hurley TD, et al. β-catenin-regulated ALDH1A1 is a target in ovarian cancer spheroids. Oncogene. 2015; 34: 2297-308.

253

Meng E, Mitra A, Tripathi K, Finan MA, Scalici J, McClellan S, et al. ALDH1A1 maintains ovarian cancer stem cell-like properties by altered regulation of cell cycle checkpoint and DNA repair network signaling. PLoS One. 2014; 9: e107142.

254

Gao F, Zhou B, Xu JC, Gao X, Li SX, Zhu GC, et al. The role of LGR5 and ALDH1A1 in non-small cell lung cancer: cancer progression and prognosis. Biochem Biophys Res Commun. 2015; 462: 91-8.

255

Ma Y, Li M, Si J, Xiong Y, Lu F, Zhang J, et al. Blockade of Notch3 inhibits the stem-like property and is associated with ALDH1A1 and CD44 via autophagy in non-small lung cancer. Int J Oncol. 2016; 48: 2349-58.

256

Shao C, Sullivan JP, Girard L, Augustyn A, Yenerall P, RodriguezCanales J, et al. Essential role of aldehyde dehydrogenase 1A3 for the maintenance of non-small cell lung cancer stem cells is associated with the STAT3 pathway. Clin Cancer Res. 2014; 20: 4154-66.

257

Sun M, Zhao H, Xiao Q, Yu Z, Song Z, Yao W, et al. Combined expression of aldehyde dehydrogenase 1A1 and β-catenin is associated with lymph node metastasis and poor survival in breast cancer patients following cyclophosphamide treatment. Oncol Rep. 2015; 34: 3163-73.

258

Thomas ML, de Antueno R, Coyle KM, Sultan M, Cruickshank BM, Giacomantonio MA, et al. Citral reduces breast tumor growth by inhibiting the cancer stem cell marker ALDH1A3. Mol Oncol. 2016; 10: 1485-96.

259

Wang W, Li Y, Liu N, Gao Y, Li L. MiR-23b controls ALDH1A1 expression in cervical cancer stem cells. BMC Cancer. 2017; 17: 292.

260

Yan Z, Xu L, Zhang J, Lu Q, Luo S, Xu L. Aldehyde dehydrogenase 1A1 stabilizes transcription factor Gli2 and enhances the activity of Hedgehog signaling in hepatocellular cancer. Biochem Biophys Res Commun. 2016; 471: 466-73.

261

Feng H, Liu Y, Bian X, Zhou F, Liu Y. ALDH1A3 affects colon cancer in vitro proliferation and invasion depending on CXCR4 status. Br J Cancer. 2018; 118: 224-32.

262

Singh S, Arcaroli J, Chen Y, Thompson DC, Messersmith W, Jimeno A, et al. ALDH1B1 Is Crucial for Colon Tumorigenesis by Modulating Wnt/β-Catenin, Notch and PI3K/Akt Signaling Pathways. PLoS One. 2015; 10: e0121648.

263

Wang X, Wang C, Zhang X, Hua R, Gan L, Huang M, et al. Bmi-1 regulates stem cell-like properties of gastric cancer cells via modulating miRNAs. J Hematol Oncol. 2016; 9: 90.

264

Jakob M, Sharaf K, Schirmer M, Leu M, Küffer S, Bertlich M, et al. Role of cancer stem cell markers ALDH1, BCL11B, BMI-1, and CD44 in the prognosis of advanced HNSCC. Strahlenther Onkol. 2021; 197: 231-45.

265

Wang J, Xing Y, Wang Y, He Y, Wang L, Peng S, et al. A novel BMI-1 inhibitor QW24 for the treatment of stem-like colorectal cancer. J Exp Clin Cancer Res. 2019; 38: 422.

266

Islam F, Gopalan V, Wahab R, Smith RA, Lam AK. Cancer stem cells in oesophageal squamous cell carcinoma: identification, prognostic and treatment perspectives. Crit Rev Oncol Hematol. 2015; 96: 9-19.

267

Hwang CC, Nieh S, Lai CH, Tsai CS, Chang LC, Hua CC, et al. A retrospective review of the prognostic value of ALDH-1, Bmi-1 and Nanog stem cell markers in esophageal squamous cell carcinoma. PLoS One. 2014; 9: e105676.

268

Liu W, Feng JQ, Shen XM, Wang HY, Liu Y, Zhou ZT. Two stem cell markers, ATP-binding cassette, G2 subfamily (ABCG2) and BMI-1, predict the transformation of oral leukoplakia to cancer: a longterm follow-up study. Cancer. 2012; 118: 1693-700.

269

Lessard J, Sauvageau G. Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature. 2003; 423: 255-60.

270

Godlewski J, Nowicki MO, Bronisz A, Williams S, Otsuki A, Nuovo G, et al. Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal. Cancer Res. 2008; 68: 9125-30.

271

Molofsky AV, Pardal R, Iwashita T, Park IK, Clarke MF, Morrison SJ. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature. 2003; 425: 962-7.

272

Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003; 63: 5821-8.

273

Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumour initiating cells. Nature. 2004; 432: 396-401.

274

Hussein D, Punjaruk W, Storer LC, Shaw L, Othman R, Peet A, et al. Pediatric brain tumor cancer stem cells: cell cycle dynamics, DNA repair, and etoposide extrusion. Neuro Oncol. 2011; 13: 70-83.

275

Zanini C, Ercole E, Mandili G, Salaroli R, Poli A, Renna C, et al. Medullospheres from DAOY, UW228 and ONS-76 cells: increased stem cell population and proteomic modifications. PLoS One. 2013; 8: e63748.

276

Iacopino F, Angelucci C, Piacentini R, Biamonte F, Mangiola A, Maira G, et al. Isolation of cancer stem cells from three human glioblastoma cell lines: characterization of two selected clones. PLoS One. 2014; 9: e105166.

277

Sana J, Zambo I, Skoda J, Neradil J, Chlapek P, Hermanova M, et al. CD133 expression and identification of CD133/nestin positive cells in rhabdomyosarcomas and rhabdomyosarcoma cell lines. Anal Cell Pathol (Amst). 2011; 34: 303-18.

278

Veselska R, Hermanova M, Loja T, Chlapek P, Zambo I, Vesely K, et al. Nestin expression in osteosarcomas and derivation of nestin/CD133 positive osteosarcoma cell lines. BMC Cancer. 2008; 8: 300.

279

Bapat SA, Mali AM, Koppikar CB, Kurrey NK. Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer. Cancer Res. 2005; 65: 3025-9.

280

Ma L, Lai D, Liu T, Cheng W, Guo L. Cancer stem-like cells can be isolated with drug selection in human ovarian cancer cell line SKOV3. Acta Biochim Biophys Sin (Shanghai). 2010; 42: 593-602.

281

He QZ, Luo XZ, Wang K, Zhou Q, Ao H, Yang Y, et al. Isolation and characterization of cancer stem cells from high-grade serous ovarian carcinomas. Cell Physiol Biochem. 2014; 33: 173-184.

282

Chiou SH, Yu CC, Huang CY, Lin SC, Liu CJ, Tsai TH, et al. Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma. Clin Cancer Res. 2008; 14: 4085-95.

283

Guzmán-Ramírez N, Völler M, Wetterwald A, Germann M, Cross NA, Rentsch CA, et al. In vitro propagation and characterization of neoplastic stem/progenitor-like cells from human prostate cancer tissue. Prostate. 2009; 69: 1683-93.

284

Liu T, Xu F, Du X, Lai D, Liu T, Zhao Y, et al. Establishment and characterization of multi-drug resistant, prostate carcinomainitiating stem-like cells from human prostate cancer cell lines 22RV1. Mol Cell Biochem. 2010; 340: 265-73.

285

Shi CJ, Gao J, Wang M, Wang X, Tian R, Zhu F, et al. CD133(+) gallbladder carcinoma cells exhibit self-renewal ability and tumorigenicity. World J Gastroenterol. 2011; 17: 2965-71.

286

Janikova M, Skarda J, Dziechciarkova M, Radova L, Chmelova J, Krejci V, et al. Identification of CD133+/nestin+ putative cancer stem cells in non-small cell lung cancer. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2010; 154: 321-6.

287

Li Y, Wang L, Pappan L, Galliher-Beckley A, Shi J. IL-1β promotes stemness and invasiveness of colon cancer cells through Zeb1 activation. Mol Cancer. 2012; 11: 87.

288

Zhao Z, Lu P, Zhang H, Xu H, Gao N, Li M, et al. Nestin positively regulates the Wnt/β-catenin pathway and the proliferation, survival and invasiveness of breast cancer stem cells. Breast Cancer Res. 2014; 16: 408.

289

Apostolou P, Toloudi M, Chatziioannou M, Ioannou E, Papasotiriou I. Cancer stem cells stemness transcription factors expression correlates with breast cancer disease stage. Curr Stem Cell Res Ther. 2012; 7: 415-9.

290

Dhingra S, Feng W, Brown RE, Zhou Z, Khoury T, Zhang R, et al. Clinicopathologic significance of putative stem cell markers, CD44 and nestin, in gastric adenocarcinoma. Int J Clin Exp Pathol. 2011; 4: 733-41.

291

Matsuda Y, Yoshimura H, Ueda J, Naito Z, Korc M, Ishiwata T. Nestin delineates pancreatic cancer stem cells in metastatic foci of NOD/Shi-scid IL2Rγ(null) (NOG) mice. Am J Pathol. 2014; 184: 674-85.

292

Sureban SM, May R, George RJ, Dieckgraefe BK, McLeod HL, Ramalingam S, et al. Knockdown of RNA binding protein musashi-1 leads to tumor regression in vivo. Gastroenterology. 2008; 134: 1448-58.

293

Ravindran G, Devaraj H. Aberrant expression of CD133 and musashi-1 in preneoplastic and neoplastic human oral squamous epithelium and their correlation with clinicopathological factors. Head Neck. 2012; 34: 1129-35.

294

Varun BR, Jayanthi P, Ramani P. Cancer stem cells: a comprehensive review on identification and therapeutic implications. J Oral Maxillofac Pathol. 2020; 24: 190.

295

Kaneko Y, Sakakibara S, Imai T, Suzuki A, Nakamura Y, Sawamoto K, et al. Musashi1: an evolutionally conserved marker for CNS progenitor cells including neural stem cells. Dev Neurosci. 2000; 22: 139-53.

296

Kikushige Y, Akashi K. TIM-3 as a therapeutic target for malignant stem cells in acute myelogenous leukemia. Ann N Y Acad Sci. 2012; 1266: 118-23.

297

Flüh C, Hattermann K, Mehdorn HM, Synowitz M, Held-Feindt J. Differential expression of CXCR4 and CXCR7 with various stem cell markers in paired human primary and recurrent glioblastomas. Int J Oncol. 2016; 48: 1408-16.

298

Miki J, Furusato B, Li H, Gu Y, Takahashi H, Egawa S, et al. Identification of putative stem cell markers, CD133 and CXCR4, in hTERT-immortalized primary nonmalignant and malignant tumor-derived human prostate epithelial cell lines and in prostate cancer specimens. Cancer Res. 2007; 67: 3153-61.

299

Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, et al. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood. 1997; 90: 5002-12.

300

Lee A, Kessler JD, Read TA, Kaiser C, Corbeil D, Huttner WB, et al. Isolation of neural stem cells from the postnatal cerebellum. Nat Neurosci. 2005; 8: 723-9.

301

Beier D, Hau P, Proescholdt M, Lohmeier A, Wischhusen J, Oefner PJ, et al. CD133(+) and CD133(-) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res. 2007; 67: 4010-5.

302

Shmelkov SV, Butler JM, Hooper AT, Hormigo A, Kushner J, Milde T, et al. CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors. J Clin Invest. 2008; 118: 2111-20.

303

Nair RM, Balla MM, Khan I, Kalathur RKR, Kondaiah P, Vemuganti GK. In vitro characterization of CD133(lo) cancer stem cells in Retinoblastoma Y79 cell line. BMC Cancer. 2017; 17: 779.

304

Hou Y, Zou Q, Ge R, Shen F, Wang Y. The critical role of CD133(+) CD44(+/high) tumor cells in hematogenous metastasis of liver cancers. Cell Res. 2012; 22: 259-72.

305

Thapa R, Wilson GD. The importance of CD44 as a stem cell biomarker and therapeutic target in cancer. Stem Cells Int. 2016; 2016: 2087204.

306

Lau WM, Teng E, Chong HS, Lopez KA, Tay AY, Salto-Tellez M, et al. CD44v8-10 is a cancer-specific marker for gastric cancer stem cells. Cancer Res. 2014; 74: 2630-41.

307

Chen W, Wang R, Zhao Y, Li Y, Wang X, Peng W, et al. CD44v6+ hepatocellular carcinoma cells maintain stemness properties through Met/cJun/Nanog signaling. Stem Cells Int. 2022; 2022: 5853707.

308

Kodama H, Murata S, Ishida M, Yamamoto H, Yamaguchi T, Kaida S, et al. Prognostic impact of CD44-positive cancer stem-like cells at the invasive front of gastric cancer. Br J Cancer. 2017; 116: 186-94.

309

Brown RL, Reinke LM, Damerow MS, Perez D, Chodosh LA, Yang J, et al. CD44 splice isoform switching in human and mouse epithelium is essential for epithelial-mesenchymal transition and breast cancer progression. J Clin Invest. 2011; 121: 1064-74.

310

Mashita N, Yamada S, Nakayama G, Tanaka C, Iwata N, Kanda M, et al. Epithelial to mesenchymal transition might be induced via CD44 isoform switching in colorectal cancer. J Surg Oncol. 2014; 110: 745-51.

311

Zhu L, Zhang W, Wang J, Liu R. Evidence of CD90+CXCR4+ cells as circulating tumor stem cells in hepatocellular carcinoma. Tumour Biol. 2015; 36: 5353-60.

312

Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007; 449: 1003-7.

313

de Sousa e Melo F, Kurtova AV, Harnoss JM, Kljavin N, Hoeck JD, Hung J, et al. A distinct role for Lgr5(+) stem cells in primary and metastatic colon cancer. Nature. 2017; 543: 676-80.

314

Leng Z, Xia Q, Chen J, Li Y, Xu J, Zhao E, et al. Lgr5+CD44+EpCAM+ strictly defines cancer stem cells in human colorectal cancer. Cell Physiol Biochem. 2018; 46: 860-72.

315

Pesce M, Schöler HR. Oct-4: gatekeeper in the beginnings of mammalian development. Stem Cells. 2001; 19: 271-8.

316

Bigdelou Z, Mortazavi Y, Saltanatpour Z, Asadi Z, Kadivar M, Johari B. Role of Oct4-Sox2 complex decoy oligodeoxynucleotides strategy on reverse epithelial to mesenchymal transition (EMT) induction in HT29-ShE encompassing enriched cancer stem-like cells. Mol Biol Rep. 2020; 47: 1859-69.

317

Zhao Y, Li C, Huang L, Niu S, Lu Q, Gong D, et al. Prognostic value of association of OCT4 with LEF1 expression in esophageal squamous cell carcinoma and their impact on epithelialmesenchymal transition, invasion, and migration. Cancer Med. 2018; 7: 3977-87.

318

Zeineddine D, Hammoud AA, Mortada M, Boeuf H. The Oct4 protein: more than a magic stemness marker. Am J Stem Cells. 2014; 3: 74-82.

319

Wang YD, Cai N, Wu XL, Cao HZ, Xie LL, Zheng PS. OCT4 promotes tumorigenesis and inhibits apoptosis of cervical cancer cells by miR-125b/BAK1 pathway. Cell Death Dis. 2013; 4: e760.

320

Kristensen DM, Nielsen JE, Kalisz M, Dalgaard MD, Audouze K, Larsen ME, et al. OCT4 and downstream factors are expressed in human somatic urogenital epithelia and in culture of epididymal spheres. Mol Hum Reprod. 2010; 16: 835-45.

321

Mamun MA, Mannoor K, Cao J, Qadri F, Song X. SOX2 in cancer stemness: tumor malignancy and therapeutic potentials. J Mol Cell Biol. 2020; 12: 85-98.

322

Wuebben EL, Rizzino A. The dark side of SOX2: cancer - a comprehensive overview. Oncotarget. 2017; 8: 44917-43.

323

Weina K, Utikal J. SOX2 and cancer: current research and its implications in the clinic. Clin Transl Med. 2014; 3: 19.

324

Mukhopadhyay A, Berrett KC, Kc U, Clair PM, Pop SM, Carr SR, et al. Sox2 cooperates with Lkb1 loss in a mouse model of squamous cell lung cancer. Cell Rep. 2014; 8: 40-9.

325

Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126: 663-76.

326

Flandez M, Guilmeau S, Blache P, Augenlicht LH. KLF4 regulation in intestinal epithelial cell maturation. Exp Cell Res. 2008; 314: 3712-23.

327

Riverso M, Montagnani V, Stecca B. KLF4 is regulated by RAS/RAF/MEK/ERK signaling through E2F1 and promotes melanoma cell growth. Oncogene. 2017; 36: 3322-33.

328

Tien YT, Chang MH, Chu PY, Lin CS, Liu CH, Liao AT. Downregulation of the KLF4 transcription factor inhibits the proliferation and migration of canine mammary tumor cells. Vet J. 2015; 205: 244-53.

329

Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, et al. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell. 2003; 113: 643-55.

330

Rodda DJ, Chew JL, Lim LH, Loh YH, Wang B, Ng HH, et al. Transcriptional regulation of nanog by OCT4 and SOX2. J Biol Chem. 2005; 280: 24731-7.

331

Alemohammad H, Asadzadeh Z, Motafakker Azad R, Hemmat N, Najafzadeh B, Vasefifar P, et al. Signaling pathways and microRNAs, the orchestrators of NANOG activity during cancer induction. Life Sci. 2020; 260: 118337.

332

Najafzadeh B, Asadzadeh Z, Motafakker Azad R, Mokhtarzadeh A, Baghbanzadeh A, Alemohammad H, et al. The oncogenic potential of NANOG: an important cancer induction mediator. J Cell Physiol. 2021; 236: 2443-58.

333

Lu X, Mazur SJ, Lin T, Appella E, Xu Y. The pluripotency factor nanog promotes breast cancer tumorigenesis and metastasis. Oncogene. 2014; 33: 2655-64.

334

Mukherjee B, Morgenbesser SD, DePinho RA. Myc family oncoproteins function through a common pathway to transform normal cells in culture: cross-interference by Max and trans-acting dominant mutants. Genes Dev. 1992; 6: 1480-92.

335

Meyer N, Penn LZ. Reflecting on 25 years with MYC. Nat Rev Cancer. 2008; 8: 976-90.

336

Dang CV. MYC, metabolism, cell growth, and tumorigenesis. Cold Spring Harb Perspect Med. 2013; 3: a014217.

337

Dang CV, O’Donnell KA, Zeller KI, Nguyen T, Osthus RC, Li F. The c-Myc target gene network. Semin Cancer Biol. 2006; 16: 253-64.

338

Chen H, Liu H, Qing G. Targeting oncogenic Myc as a strategy for cancer treatment. Signal Transduct Target Ther. 2018; 3: 5.

339

Clay MR, Tabor M, Owen JH, Carey TE, Bradford CR, Wolf GT, et al. Single-marker identification of head and neck squamous cell carcinoma cancer stem cells with aldehyde dehydrogenase. Head Neck. 2010; 32: 1195-201.

340

Sullivan JP, Spinola M, Dodge M, Raso MG, Behrens C, Gao B, et al. Aldehyde dehydrogenase activity selects for lung adenocarcinoma stem cells dependent on notch signaling. Cancer Res. 2010; 70: 9937-48.

341

Blume R, Rempel E, Manta L, Saeed BR, Wang W, Raffel S, et al. The molecular signature of AML with increased ALDH activity suggests a stem cell origin. Leuk Lymphoma. 2018; 59: 2201-10.

342

Chen D, Wu M, Li Y, Chang I, Yuan Q, Ekimyan-Salvo M, et al. Targeting BMI1(+) cancer stem cells overcomes chemoresistance and inhibits metastases in squamous cell carcinoma. Cell Stem Cell. 2017; 20: 621-34.e626.

343

Siddique HR, Saleem M. Role of BMI1, a stem cell factor, in cancer recurrence and chemoresistance: preclinical and clinical evidences. Stem Cells. 2012; 30: 372-8.

344

Shen HT, Chien PJ, Chen SH, Sheu GT, Jan MS, Wang BY, et al. BMI1-mediated pemetrexed resistance in non-small cell lung cancer cells is associated with increased SP1 activation and cancer stemness. Cancers (Basel) 2020; 12: 2069.

345

Liu S, Dontu G, Mantle ID, Patel S, Ahn NS, Jackson KW, et al. Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res. 2006; 66: 6063-71.

346

Lendahl U, Zimmerman LB, McKay RD. CNS stem cells express a new class of intermediate filament protein. Cell. 1990; 60: 585-95.

347

Kanemura Y, Mori K, Sakakibara S, Fujikawa H, Hayashi H, Nakano A, et al. Musashi1, an evolutionarily conserved neural RNA-binding protein, is a versatile marker of human glioma cells in determining their cellular origin, malignancy, and proliferative activity. Differentiation. 2001; 68: 141-52.

348

Toda M, Iizuka Y, Yu W, Imai T, Ikeda E, Yoshida K, et al. Expression of the neural RNA-binding protein Musashi1 in human gliomas. Glia. 2001; 34: 1-7.

349

Glazer RI, Vo DT, Penalva LO. Musashi1: an RBP with versatile functions in normal and cancer stem cells. Front Biosci (Landmark Ed). 2012; 17: 54-64.

350

Tang D, Lotze MT. Tumor immunity times out: TIM-3 and HMGB1. Nat Immunol. 2012; 13: 808-10.

351

Cheng L, Ruan Z. Tim-3 and Tim-4 as the potential targets for antitumor therapy. Hum Vaccin Immunother. 2015; 11: 2458-62.

352

Mollica Poeta V, Massara M, Capucetti A, Bonecchi R. Chemokines and chemokine receptors: new targets for cancer immunotherapy. Front Immunol. 2019; 10: 379.

353

Do HTT, Lee CH, Cho J. Chemokines and their receptors: multifaceted roles in cancer progression and potential value as cancer prognostic markers. Cancers (Basel) 2020; 12: 287.

354

Bachelerie F, Ben-Baruch A, Burkhardt AM, Combadiere C, Farber JM, Graham GJ, et al. International Union of Basic and Clinical Pharmacology.[corrected]. LXXXIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors. Pharmacol Rev. 2014; 66: 1-79.

355

Hopman RK, DiPersio JF. Advances in stem cell mobilization. Blood Rev. 2014; 28: 31-40.

356

Sugiyama T, Kohara H, Noda M, Nagasawa T. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity. 2006; 25: 977-88.

357

Dubrovska A, Elliott J, Salamone RJ, Telegeev GD, Stakhovsky AE, Schepotin IB, et al. CXCR4 expression in prostate cancer progenitor cells. PLoS One. 2012; 7: e31226.

358

Zhang SS, Han ZP, Jing YY, Tao SF, Li TJ, Wang H, et al. CD133(+) CXCR4(+) colon cancer cells exhibit metastatic potential and predict poor prognosis of patients. BMC Med. 2012; 10: 85.

359

Sharanek A, Burban A, Laaper M, Heckel E, Joyal JS, Soleimani VD, et al. OSMR controls glioma stem cell respiration and confers resistance of glioblastoma to ionizing radiation. Nat Commun. 2020; 11: 4116.

360

Clara JA, Monge C, Yang Y, Takebe N. Targeting signalling pathways and the immune microenvironment of cancer stem cells - a clinical update. Nat Rev Clin Oncol. 2020; 17: 204-32.

361

Manni W, Min W. Signaling pathways in the regulation of cancer stem cells and associated targeted therapy. MedComm (2020). 2022; 3: e176.

362

Wang K, Zhang T, Dong Q, Nice EC, Huang C, Wei Y. Redox homeostasis: the linchpin in stem cell self-renewal and differentiation. Cell Death Dis. 2013; 4: e537.

363

Chen Z, Shi T, Zhang L, Zhu P, Deng M, Huang C, et al. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: a review of the past decade. Cancer Lett. 2016; 370: 153-64.

364

Kazi JU. Mechanisms of anticancer therapy resistance: the role of cancer stem cells. Int J Mol Sci. 2020; 21: 9006.

365

Hou H, Sun H, Lu P, Ge C, Zhang L, Li H, et al. Tunicamycin potentiates cisplatin anticancer efficacy through the DPAGT1/Akt/ABCG2 pathway in mouse Xenograft models of human hepatocellular carcinoma. Mol Cancer Ther. 2013; 12: 2874-84.

366

Hu L, Liang Y, Wu K, Wang C, Zhang T, Peng R, et al. Repressing PDCD4 activates JNK/ABCG2 pathway to induce chemoresistance to fluorouracil in colorectal cancer cells. Ann Transl Med. 2021; 9: 114.

367

Yao XH, Ping YF, Bian XW. Contribution of cancer stem cells to tumor vasculogenic mimicry. Protein Cell. 2011; 2: 266-72.

368

Liu TJ, Sun BC, Zhao XL, Zhao XM, Sun T, Gu Q, et al. CD133+ cells with cancer stem cell characteristics associates with vasculogenic mimicry in triple-negative breast cancer. Oncogene. 2013; 32: 544-53.

369

Zheng N, Zhang S, Wu W, Zhang N, Wang J. Regulatory mechanisms and therapeutic targeting of vasculogenic mimicry in hepatocellular carcinoma. Pharmacol Res. 2021; 166: 105507.

370

Sun H, Yao N, Cheng S, Li L, Liu S, Yang Z, et al. Cancer stem-like cells directly participate in vasculogenic mimicry channels in triple-negative breast cancer. Cancer Biol Med. 2019; 16: 299-311.

371

de Jong MC, Pramana J, van der Wal JE, Lacko M, Peutz-Kootstra CJ, de Jong JM, et al. CD44 expression predicts local recurrence after radiotherapy in larynx cancer. Clin Cancer Res. 2010; 16: 5329-38.

372

Duru N, Fan M, Candas D, Menaa C, Liu HC, Nantajit D, et al. HER2-associated radioresistance of breast cancer stem cells isolated from HER2-negative breast cancer cells. Clin Cancer Res. 2012; 18: 6634-47.

373

Desai A, Webb B, Gerson SL. CD133+ cells contribute to radioresistance via altered regulation of DNA repair genes in human lung cancer cells. Radiother Oncol. 2014; 110: 538-45.

374

Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006; 444: 756-60.

375

Ahmed SU, Carruthers R, Gilmour L, Yildirim S, Watts C, Chalmers AJ. Selective inhibition of parallel DNA damage response pathways optimizes radiosensitization of glioblastoma stem-like cells. Cancer Res. 2015; 75: 4416-28.

376

Wu J, Lai G, Wan F, Xiao Z, Zeng L, Wang X, et al. Knockdown of checkpoint kinase 1 is associated with the increased radiosensitivity of glioblastoma stem-like cells. Tohoku J Exp Med. 2012; 226: 267-74.

377

Carruthers R, Ahmed SU, Strathdee K, Gomez-Roman N, Amoah-Buahin E, Watts C, et al. Abrogation of radioresistance in glioblastoma stem-like cells by inhibition of ATM kinase. Mol Oncol. 2015; 9: 192-203.

378

Wang X, Ma Z, Xiao Z, Liu H, Dou Z, Feng X, et al. Chk1 knockdown confers radiosensitization in prostate cancer stem cells. Oncol Rep. 2012; 28: 2247-54.

379

Yin H, Glass J. The phenotypic radiation resistance of CD44+/CD24(- or low) breast cancer cells is mediated through the enhanced activation of ATM signaling. PLoS One. 2011; 6: e24080.

380

Park SY, Lee CJ, Choi JH, Kim JH, Kim JW, Kim JY, et al. The JAK2/STAT3/CCND2 axis promotes colorectal Cancer stem cell persistence and radioresistance. J Exp Clin Cancer Res. 2019; 38: 399.

381

Lomonaco SL, Finniss S, Xiang C, Decarvalho A, Umansky F, Kalkanis SN, et al. The induction of autophagy by gammaradiation contributes to the radioresistance of glioma stem cells. Int J Cancer. 2009; 125: 717-22.

382

Seidel S, Garvalov BK, Wirta V, von Stechow L, Schanzer A, Meletis K, et al. A hypoxic niche regulates glioblastoma stem cells through hypoxia inducible factor 2 alpha. Brain. 2010; 133: 983-95.

383

Nagaraju GP, Bramhachari PV, Raghu G, El-Rayes BF. Hypoxia inducible factor-1alpha: its role in colorectal carcinogenesis and metastasis. Cancer Lett. 2015; 366: 11-8.

384

Yang Z, Han Y, Cheng K, Zhang G, Wang X. miR-99a directly targets the mTOR signalling pathway in breast cancer side population cells. Cell Prolif. 2014; 47: 587-95.

385

Chen X, Wu L, Li D, Xu Y, Zhang L, Niu K, et al. Radiosensitizing effects of miR-18a-5p on lung cancer stem-like cells via downregulating both ATM and HIF-1alpha. Cancer Med. 2018; 7: 3834-47.

386

Li MY, Fan LN, Han DH, Yu Z, Ma J, Liu YX, et al. Ribosomal S6 protein kinase 4 promotes radioresistance in esophageal squamous cell carcinoma. J Clin Invest. 2020; 130: 4301-19.

387

Chang L, Graham P, Hao J, Ni J, Deng J, Bucci J, et al. Cancer stem cells and signaling pathways in radioresistance. Oncotarget. 2016; 7: 11002-17.

388

Karabicici M, Alptekin S, Fırtına Karagonlar Z, Erdal E. Doxorubicin-induced senescence promotes stemness and tumorigenicity in EpCAM-/CD133- nonstem cell population in hepatocellular carcinoma cell line, HuH-7. Mol Oncol. 2021; 15: 2185-202.

389

Piva M, Domenici G, Iriondo O, Rábano M, Simões BM, Comaills V, et al. Sox2 promotes tamoxifen resistance in breast cancer cells. EMBO Mol Med. 2014; 6: 66-79.

390

Ahmad A, Maitah MY, Ginnebaugh KR, Li Y, Bao B, Gadgeel SM, et al. Inhibition of Hedgehog signaling sensitizes NSCLC cells to standard therapies through modulation of EMT-regulating miRNAs. J Hematol Oncol. 2013; 6: 77.

391

Sarvi S, Mackinnon AC, Avlonitis N, Bradley M, Rintoul RC, Rassl DM, et al. CD133+ cancer stem-like cells in small cell lung cancer are highly tumorigenic and chemoresistant but sensitive to a novel neuropeptide antagonist. Cancer Res. 2014; 74: 1554-65.

392

Jiang F, Qiu Q, Khanna A, Todd NW, Deepak J, Xing L, et al. Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol Cancer Res. 2009; 7: 330-8.

393

Wang W, Wang J, Liu S, Ren Y, Wang J, Liu S, et al. An EHMT2/NFYA-ALDH2 signaling axis modulates the RAF pathway to regulate paclitaxel resistance in lung cancer. Mol Cancer. 2022; 21: 106.

394

Liu YP, Yang CJ, Huang MS, Yeh CT, Wu AT, Lee YC, et al. Cisplatin selects for multidrug-resistant CD133+ cells in lung adenocarcinoma by activating Notch signaling. Cancer Res. 2013; 73: 406-16.

395

Hashida S, Yamamoto H, Shien K, Miyoshi Y, Ohtsuka T, Suzawa K, et al. Acquisition of cancer stem cell-like properties in non-small cell lung cancer with acquired resistance to afatinib. Cancer Sci. 2015; 106: 1377-84.

396

Chen YJ, Huang WC, Wei YL, Hsu SC, Yuan P, Lin HY, et al. Elevated BCRP/ABCG2 expression confers acquired resistance to gefitinib in wild-type EGFR-expressing cells. PLoS One. 2011; 6: e21428.

397

Song J, Xie LX, Zhang XY, Hu P, Long MF, Xiong F, et al. Role of YAP in lung cancer resistance to cisplatin. Oncol Lett. 2018; 16: 3949-54.

398

Chen MJ, Wu DW, Wang YC, Chen CY, Lee H. PAK1 confers chemoresistance and poor outcome in non-small cell lung cancer via β-catenin-mediated stemness. Sci Rep. 2016; 6: 34933.

399

Zhang Y, Xu W, Guo H, Zhang Y, He Y, Lee SH, et al. NOTCH1 signaling regulates self-renewal and platinum chemoresistance of cancer stem-like cells in human non-small cell lung cancer. Cancer Res. 2017; 77: 3082-91.

400

Li J, Ye T, Liu Y, Kong L, Sun Z, Liu D, et al. Transcriptional activation of Gstp1 by MEK/ERK signaling confers chemo-resistance to cisplatin in lung cancer stem cells. Front Oncol. 2019; 9: 476.

401

Zhang J, Liu J, Li H, Wang J. β-catenin signaling pathway regulates cisplatin resistance in lung adenocarcinoma cells by upregulating Bcl-xl. Mol Med Rep. 2016; 13: 2543-51.

402

Yang J, Zhang K, Wu J, Shi J, Xue J, Li J, et al. Wnt5a increases properties of lung cancer stem cells and resistance to cisplatin through activation of Wnt5a/PKC signaling pathway. Stem Cells Int. 2016; 2016: 1690896.

403

Zhang P, Ma Y, Lv C, Huang M, Li M, Dong B, et al. Upregulation of programmed cell death ligand 1 promotes resistance response in non-small-cell lung cancer patients treated with neo-adjuvant chemotherapy. Cancer Sci. 2016; 107: 1563-71.

404

Koh H, Park H, Chandimali N, Huynh DL, Zhang JJ, Ghosh M, et al. MicroRNA-128 suppresses paclitaxel-resistant lung cancer by inhibiting MUC1-C and BMI-1 in cancer stem cells. Oncotarget. 2017; 8: 110540-51.

405

Ma Z, Cai H, Zhang Y, Chang L, Cui Y. MiR-129-5p inhibits nonsmall cell lung cancer cell stemness and chemoresistance through targeting DLK1. Biochem Biophys Res Commun. 2017; 490: 309-16.

406

Park CR, Lee M, Lee SY, Kang D, Park SJ, Lee DC, et al. Regulating POLR3G by MicroRNA-26a-5p as a promising therapeutic target of lung cancer stemness and chemosensitivity. Noncoding RNA Res. 2023; 8: 273-81.

407

Chandimali N, Koh H, Kim J, Lee J, Park YH, Sun HN, et al. BRM270 targets cancer stem cells and augments chemo-sensitivity in cancer. Oncol Lett. 2020; 20: 103.

408

Yang L, Shi P, Zhao G, Xu J, Peng W, Zhang J, et al. Targeting cancer stem cell pathways for cancer therapy. Signal Transduct Target Ther. 2020; 5: 8.

409

Lee JW, Lee HY. Targeting cancer stem cell markers or pathways: a potential therapeutic strategy for oral cancer treatment. Int J Stem Cells. 2021; 14: 386-99.

410

Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015; 348: 56-61.

411

Kaumaya PTP, Guo L, Overholser J, Penichet ML, Bekaii-Saab T. Immunogenicity and antitumor efficacy of a novel human PD-1 B-cell vaccine (PD1-Vaxx) and combination immunotherapy with dual trastuzumab/pertuzumab-like HER-2 B-cell epitope vaccines (B-Vaxx) in a syngeneic mouse model. Oncoimmunology. 2020; 9: 1818437.

412

Rekoske BT, McNeel DG. Immunotherapy for prostate cancer: false promises or true hope? Cancer. 2016; 122: 3598-607.

413

Deng Z, Wu Y, Ma W, Zhang S, Zhang YQ. Adoptive T-cell therapy of prostate cancer targeting the cancer stem cell antigen EpCAM. BMC Immunol. 2015; 16: 1.

414

Zhang BL, Li D, Gong YL, Huang Y, Qin DY, Jiang L, et al. Preclinical evaluation of chimeric antigen receptor-modified T cells specific to epithelial cell adhesion molecule for treating colorectal cancer. Hum Gene Ther. 2019; 30: 402-12.

415

Chen HC, Joalland N, Bridgeman JS, Alchami FS, Jarry U, Khan MWA, et al. Synergistic targeting of breast cancer stem-like cells by human γδ T cells and CD8(+) T cells. Immunol Cell Biol. 2017; 95: 620-9.

416

Cook M, Chauhan A. Clinical application of oncolytic viruses: a systematic review. Int J Mol Sci. 2020; 21: 7505.

417

Wang H, Chen NG, Minev BR, Szalay AA. Oncolytic vaccinia virus GLV-1h68 strain shows enhanced replication in human breast cancer stem-like cells in comparison to breast cancer cells. J Transl Med. 2012; 10: 167.

418

Tomasicchio M, Semple L, Esmail A, Meldau R, Randall P, Pooran A, et al. An autologous dendritic cell vaccine polarizes a Th-1 response which is tumoricidal to patient-derived breast cancer cells. Cancer Immunol Immunother. 2019; 68: 71-83.

419

Dashti A, Ebrahimi M, Hadjati J, Memarnejadian A, Moazzeni SM. Dendritic cell based immunotherapy using tumor stem cells mediates potent antitumor immune responses. Cancer Lett. 2016; 374: 175-85.

420

Yin T, Shi P, Gou S, Shen Q, Wang C. Dendritic cells loaded with pancreatic Cancer Stem Cells (CSCs) lysates induce antitumor immune killing effect in vitro. PLoS One. 2014; 9: e114581.

421

Wefers C, Schreibelt G, Massuger L, de Vries IJM, Torensma R. Immune curbing of cancer stem cells by CTLs directed to NANOG. Front Immunol. 2018; 9: 1412.

422

Hu Y, Lu L, Xia Y, Chen X, Chang AE, Hollingsworth RE, et al. Therapeutic efficacy of cancer stem cell vaccines in the adjuvant setting. Cancer Res. 2016; 76: 4661-72.

423

Guo F, Zhang Y, Bai L, Cui J. Natural killer cell therapy targeting cancer stem cells: old wine in a new bottle. Cancer Lett. 2023; 570: 216328.

424

Klapdor R, Wang S, Hacker U, Büning H, Morgan M, Dörk T, et al. Improved killing of ovarian cancer stem cells by combining a novel chimeric antigen receptor-based immunotherapy and chemotherapy. Hum Gene Ther. 2017; 28: 886-96.

425

Hu X, Li J, Fu M, Zhao X, Wang W. The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct Target Ther. 2021; 6: 402.

426

Shiah JV, Grandis JR, Johnson DE. Targeting STAT3 with proteolysis targeting chimeras and next-generation antisense oligonucleotides. Mol Cancer Ther. 2021; 20: 219-28.

427

Chen B, Dai W, Mei D, Liu T, Li S, He B, et al. Comprehensively priming the tumor microenvironment by cancer-associated fibroblast-targeted liposomes for combined therapy with cancer cell-targeted chemotherapeutic drug delivery system. J Control Release. 2016; 241: 68-80.

428

Annibaldi A, Widmann C. Glucose metabolism in cancer cells. Curr Opin Clin Nutr Metab Care. 2010; 13: 466-70.

429

Krasnov GS, Dmitriev AA, Snezhkina AV, Kudryavtseva AV. Deregulation of glycolysis in cancer: glyceraldehyde-3-phosphate dehydrogenase as a therapeutic target. Expert Opin Ther Targets. 2013; 17: 681-93.

430

Ceradini DJ, Kulkarni AR, Callaghan MJ, Tepper OM, Bastidas N, Kleinman ME, et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004; 10: 858-64.

431

Kao TW, Chuang YC, Lee HL, Kuo CC, Shen YA. Therapeutic targeting of glutaminolysis as a novel strategy to combat cancer stem cells. Int J Mol Sci. 2022; 23: 15296.

432

Shibuya K, Okada M, Suzuki S, Seino M, Seino S, Takeda H, et al. Targeting the facilitative glucose transporter GLUT1 inhibits the self-renewal and tumor-initiating capacity of cancer stem cells. Oncotarget. 2015; 6: 651-61.

433

Wu K, Ning Z, Zeng J, Fan J, Zhou J, Zhang T, et al. Silibinin inhibits β-catenin/ZEB1 signaling and suppresses bladder cancer metastasis via dual-blocking epithelial-mesenchymal transition and stemness. Cell Signal. 2013; 25: 2625-33.

434

Flaig TW, Gustafson DL, Su LJ, Zirrolli JA, Crighton F, Harrison GS, et al. A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients. Invest New Drugs. 2007; 25: 139-46.

435

Shen YA, Chen CC, Chen BJ, Wu YT, Juan JR, Chen LY, et al. Potential therapies targeting metabolic pathways in cancer stem cells. Cells. 2021; 10: 1772.

436

Roesch A, Vultur A, Bogeski I, Wang H, Zimmermann KM, Speicher D, et al. Overcoming intrinsic multidrug resistance in melanoma by blocking the mitochondrial respiratory chain of slow-cycling JARID1B(high) cells. Cancer Cell. 2013; 23: 811-25.

437

Lamb R, Ozsvari B, Lisanti CL, Tanowitz HB, Howell A, MartinezOutschoorn UE, et al. Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: treating cancer like an infectious disease. Oncotarget. 2015; 6: 4569-84.

438

Fiorillo M, Lamb R, Tanowitz HB, Mutti L, Krstic-Demonacos M, Cappello AR, et al. Repurposing atovaquone: targeting mitochondrial complex Ⅲ and OXPHOS to eradicate cancer stem cells. Oncotarget. 2016; 7: 34084-99.

439

Lamb R, Harrison H, Hulit J, Smith DL, Lisanti MP, Sotgia F. Mitochondria as new therapeutic targets for eradicating cancer stem cells: quantitative proteomics and functional validation via MCT1/2 inhibition. Oncotarget. 2014; 5: 11029-37.

440

An H, Kim JY, Oh E, Lee N, Cho Y, Seo JH. Salinomycin promotes anoikis and decreases the CD44+/CD24- stem-like population via inhibition of STAT3 activation in MDA-MB-231 Cells. PLoS One. 2015; 10: e0141919.

441

Chu DJ, Yao DE, Zhuang YF, Hong Y, Zhu XC, Fang ZR, et al. Azithromycin enhances the favorable results of paclitaxel and cisplatin in patients with advanced non-small cell lung cancer. Genet Mol Res. 2014; 13: 2796-805.

442

Jung JW, Park SB, Lee SJ, Seo MS, Trosko JE, Kang KS. Metformin represses self-renewal of the human breast carcinoma stem cells via inhibition of estrogen receptor-mediated OCT4 expression. PLoS One. 2011; 6: e28068.

443

Mukha A, Kahya U, Dubrovska A. Targeting glutamine metabolism and autophagy: the combination for prostate cancer radiosensitization. Autophagy. 2021; 17: 3879-81.

444

Jariyal H, Gupta C, Andhale S, Gadge S, Srivastava A. Comparative stemness and differentiation of luminal and basal breast cancer stem cell type under glutamine-deprivation. J Cell Commun Signal. 2021; 15: 207-22.

445

Zhu J, Wang H, Sun Q, Ji X, Zhu L, Cong Z, et al. Nrf2 is required to maintain the self-renewal of glioma stem cells. BMC Cancer. 2013; 13: 380.

446

Zhu J, Wang H, Fan Y, Hu Y, Ji X, Sun Q, et al. Knockdown of nuclear factor erythroid 2-related factor 2 by lentivirus induces differentiation of glioma stem-like cells. Oncol Rep. 2014; 32: 1170-8.

447

Ryoo IG, Choi BH, Kwak MK. Activation of NRF2 by p62 and proteasome reduction in sphere-forming breast carcinoma cells. Oncotarget. 2015; 6: 8167-84.

448

Ryoo IG, Lee SH, Kwak MK. Redox modulating NRF2: a potential mediator of cancer stem cell resistance. Oxid Med Cell Longev. 2016; 2016: 2428153.

449

Ouyang WC, Liao YW, Chen PN, Lu KH, Yu CC, Hsieh PL. Hinokitiol suppresses cancer stemness and oncogenicity in glioma stem cells by Nrf2 regulation. Cancer Chemother Pharmacol. 2017; 80: 411-9.

450

Woo Y, Oh J, Kim JS. Suppression of Nrf2 activity by chestnut leaf extract increases chemosensitivity of breast cancer stem cells to paclitaxel. Nutrients. 2017; 9: 760.

451

Cheng G, Palanisamy AP, Evans ZP, Sutter AG, Jin L, Singh I, et al. Cerulenin blockade of fatty acid synthase reverses hepatic steatosis in ob/ob mice. PLoS One. 2013; 8: e75980.

452

Van de Sande T, De Schrijver E, Heyns W, Verhoeven G, Swinnen JV. Role of the phosphatidylinositol 3’-kinase/PTEN/Akt kinase pathway in the overexpression of fatty acid synthase in LNCaP prostate cancer cells. Cancer Res. 2002; 62: 642-6.

453

Colacino JA, McDermott SP, Sartor MA, Wicha MS, Rozek LS. Transcriptomic profiling of curcumin-treated human breast stem cells identifies a role for stearoyl-coa desaturase in breast cancer prevention. Breast Cancer Res Treat. 2016; 158: 29-41.

454

Li J, Condello S, Thomes-Pepin J, Ma X, Xia Y, Hurley TD, et al. Lipid desaturation is a metabolic marker and therapeutic target of ovarian cancer stem cells. Cell Stem Cell. 2017; 20: 303-14.e305.

455

Elgendy SM, Alyammahi SK, Alhamad DW, Abdin SM, Omar HA. Ferroptosis: an emerging approach for targeting cancer stem cells and drug resistance. Crit Rev Oncol Hematol. 2020; 155: 103095.

456

Lim YC, Kang HJ, Kim YS, Choi EC. All-trans-retinoic acid inhibits growth of head and neck cancer stem cells by suppression of Wnt/β-catenin pathway. Eur J Cancer. 2012; 48: 3310-18.

457

Luo C, Ding Z, Tu Y, Tan J, Luo Q, Song G. Biomaterial-based platforms for cancer stem cell enrichment and study. Cancer Biol Med. 2021; 18: 458-69.

458

Li R, Chen Z, Dai Z, Yu Y. Nanotechnology assisted photo- and sonodynamic therapy for overcoming drug resistance. Cancer Biol Med. 2021; 18: 388-400.

Cancer Biology & Medicine
Pages 985-1020
Cite this article:
Zhang S, Yang R, Ouyang Y, et al. Cancer stem cells: a target for overcoming therapeutic resistance and relapse. Cancer Biology & Medicine, 2023, 20(12): 985-1020. https://doi.org/10.20892/j.issn.2095-3941.2023.0333

288

Views

5

Downloads

0

Crossref

0

Web of Science

0

Scopus

Altmetrics

Received: 04 September 2023
Accepted: 20 November 2023
Published: 05 February 2024
©2023 Cancer Biology & Medicine.

Creative Commons Attribution-NonCommercial 4.0 International License

Return