AI Chat Paper
Discover the SciOpen Platform and Achieve Your Research Goals with Ease.
Search articles, authors, keywords, DOl and etc.
{{expandStatus?'Exit ':''}}Advanced Search
(
Among central nervous system-associated malignancies, glioblastoma (GBM) is the most common and has the highest mortality rate. The high heterogeneity of GBM cell types and the complex tumor microenvironment frequently lead to tumor recurrence and sudden relapse in patients treated with temozolomide. In precision medicine, research on GBM treatment is increasingly focusing on molecular subtyping to precisely characterize the cellular and molecular heterogeneity, as well as the refractory nature of GBM toward therapy. Deep understanding of the different molecular expression patterns of GBM subtypes is critical. Researchers have recently proposed tetra fractional or tripartite methods for detecting GBM molecular subtypes. The various molecular subtypes of GBM show significant differences in gene expression patterns and biological behaviors. These subtypes also exhibit high plasticity in their regulatory pathways, oncogene expression, tumor microenvironment alterations, and differential responses to standard therapy. Herein, we summarize the current molecular typing scheme of GBM and the major molecular/genetic characteristics of each subtype. Furthermore, we review the mesenchymal transition mechanisms of GBM under various regulators.
Uddin MS, Mamun AA, Alghamdi BS, Tewari D, Jeandet P, Sarwar MS, et al. Epigenetics of glioblastoma multiforme: from molecular mechanisms to therapeutic approaches. Semin Cancer Biol. 2022; 83: 100-20.
Cui X, Wang Y, Zhou J, Wang Q, Kang C. Expert opinion on translational research for advanced glioblastoma treatment. Cancer Biol Med. 2023; 20: 344-52.
Dunn GP, Rinne ML, Wykosky J, Genovese G, Quayle SN, Dunn IF, et al. Emerging insights into the molecular and cellular basis of glioblastoma. Genes Dev. 2012; 26: 756-84.
Olar A, Aldape KD. Using the molecular classification of glioblastoma to inform personalized treatment. J Pathol. 2014; 232: 165-77.
Noushmehr H, Weisenberger DJ, Diefes K, Phillips HS, Pujara K, Berman BP, et al. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell. 2010; 17: 510-22.
Dejaegher J, Solie L, Hunin Z, Sciot R, Capper D, Siewert C, et al. DNA methylation based glioblastoma subclassification is related to tumoral T-cell infiltration and patient survival. Neuro Oncol. 2021; 23: 240-50.
Ma H, Zhao C, Zhao Z, Hu L, Ye F, Wang H, et al. Specific glioblastoma multiforme prognostic-subtype distinctions based on DNA methylation patterns. Cancer Gene Ther. 2020; 27: 702-14.
Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD, et al. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell. 2006; 9: 157-73.
Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010; 17: 98-110.
Wang Q, Hu B, Hu X, Kim H, Squatrito M, Scarpace L, et al. Tumor evolution of glioma-intrinsic gene expression subtypes associates with immunological changes in the microenvironment. Cancer Cell. 2017; 32: 42-56.e6.
Bhat KPL, Balasubramaniyan V, Vaillant B, Ezhilarasan R, Hummelink K, Hollingsworth F, et al. Mesenchymal differentiation mediated by NF-kappaB promotes radiation resistance in glioblastoma. Cancer Cell. 2013; 24: 331-46.
Behnan J, Finocchiaro G, Hanna G. The landscape of the mesenchymal signature in brain tumours. Brain. 2019; 142: 847-66.
Azam Z, To ST, Tannous BA. Mesenchymal transformation: the rosetta stone of glioblastoma pathogenesis and therapy resistance. Adv Sci (Weinh). 2020; 7: 2002015.
Segerman A, Niklasson M, Haglund C, Bergstrom T, Jarvius M, Xie Y, et al. Clonal variation in drug and radiation response among glioma-initiating cells is linked to proneural-mesenchymal transition. Cell Rep. 2016; 17: 2994-3009.
Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021; 23: 1231-51.
Jankowska S, Lewandowska M, Masztalewicz M, Sagan L, Nowacki P, Urasinska E. Molecular classification of glioblastoma based on immunohistochemical expression of EGFR, PDGFRA, NF1, IDH1, p53 and PTEN proteins. Pol J Pathol. 2021; 72: 1-10.
Le Mercier M, Hastir D, Moles Lopez X, De Neve N, Maris C, Trepant AL, et al. A simplified approach for the molecular classification of glioblastomas. PLoS One. 2012; 7: e45475.
Popova SN, Bergqvist M, Dimberg A, Edqvist PH, Ekman S, Hesselager G, et al. Subtyping of gliomas of various WHO grades by the application of immunohistochemistry. Histopathology. 2014; 64: 365-79.
Le NQK, Hung TNK, Do DT, Lam LHT, Dang LH, Huynh TT. Radiomics-based machine learning model for efficiently classifying transcriptome subtypes in glioblastoma patients from MRI. Comput Biol Med. 2021; 132: 104320.
Yang D, Rao G, Martinez J, Veeraraghavan A, Rao A. Evaluation of tumor-derived MRI-texture features for discrimination of molecular subtypes and prediction of 12-month survival status in glioblastoma. Med Phys. 2015; 42: 6725-35.
Ozawa T, Riester M, Cheng YK, Huse JT, Squatrito M, Helmy K, et al. Most human non-GCIMP glioblastoma subtypes evolve from a common proneural-like precursor glioma. Cancer Cell. 2014; 26: 288-300.
Wang L, Babikir H, Muller S, Yagnik G, Shamardani K, Catalan F, et al. The phenotypes of proliferating glioblastoma cells reside on a single axis of variation. Cancer Discov. 2019; 9: 1708-19.
Chelebian E, Fuster-Garcia E, Alvarez-Torres MDM, Juan-Albarracin J, Garcia-Gomez JM. Higher vascularity at infiltrated peripheral edema differentiates proneural glioblastoma subtype. PLoS One. 2020; 15: e0232500.
Rahme GJ, Luikart BW, Cheng C, Israel MA. A recombinant lentiviral PDGF-driven mouse model of proneural glioblastoma. Neuro Oncol. 2018; 20: 332-42.
Almiron Bonnin DA, Ran C, Havrda MC, Liu H, Hitoshi Y, Zhang Z, et al. Insulin-mediated signaling facilitates resistance to PDGFR inhibition in proneural hPDGFB-driven gliomas. Mol Cancer Ther. 2017; 16: 705-16.
Park MG, Seo S, Ham SW, Choi SH, Kim H. Dihydropyrimidinase-related protein 5 controls glioblastoma stem cell characteristics as a biomarker of proneural-subtype glioblastoma stem cells. Oncol Lett. 2020; 20: 1153-62.
Guadagno E, Vitiello M, Francesca P, Cali G, Caponnetto F, Cesselli D, et al. PATZ1 is a new prognostic marker of glioblastoma associated with the stem-like phenotype and enriched in the proneural subtype. Oncotarget. 2017; 8: 59282-300.
He X, Zhang S, Chen J, Li D. Increased LGALS3 expression independently predicts shorter overall survival in patients with the proneural subtype of glioblastoma. Cancer Med. 2019; 8: 2031-40.
Lescarbeau RS, Lei L, Bakken KK, Sims PA, Sarkaria JN, Canoll P, et al. Quantitative phosphoproteomics reveals Wee1 kinase as a therapeutic target in a model of proneural glioblastoma. Mol Cancer Ther. 2016; 15: 1332-43.
Hai L, Zhang C, Li T, Zhou X, Liu B, Li S, et al. Notch1 is a prognostic factor that is distinctly activated in the classical and proneural subtype of glioblastoma and that promotes glioma cell survival via the NF-kappaB(p65) pathway. Cell Death Dis. 2018; 9: 158.
Jin X, Kim LJY, Wu Q, Wallace LC, Prager BC, Sanvoranart T, et al. Targeting glioma stem cells through combined BMI1 and EZH2 inhibition. Nat Med. 2017; 23: 1352-61.
Pan YB, Wang S, Yang B, Jiang Z, Lenahan C, Wang J, et al. Transcriptome analyses reveal molecular mechanisms underlying phenotypic differences among transcriptional subtypes of glioblastoma. J Cell Mol Med. 2020; 24: 3901-16.
Niklasson M, Bergstrom T, Jarvius M, Sundstrom A, Nyberg F, Haglund C, et al. Mesenchymal transition and increased therapy resistance of glioblastoma cells is related to astrocyte reactivity. J Pathol. 2019; 249: 295-307.
Wang Q, Cai J, Fang C, Yang C, Zhou J, Tan Y, et al. Mesenchymal glioblastoma constitutes a major ceRNA signature in the TGF-beta pathway. Theranostics. 2018; 8: 4733-49.
Cooper LA, Gutman DA, Chisolm C, Appin C, Kong J, Rong Y, et al. The tumor microenvironment strongly impacts master transcriptional regulators and gene expression class of glioblastoma. Am J Pathol. 2012; 180: 2108-19.
Zhao K, Cui X, Wang Q, Fang C, Tan Y, Wang Y, et al. RUNX1 contributes to the mesenchymal subtype of glioblastoma in a TGFbeta pathway-dependent manner. Cell Death Dis. 2019; 10: 877.
Higa N, Shinsato Y, Kamil M, Hirano T, Takajo T, Shimokawa M, et al. Formin-like 1 (FMNL1) is associated with glioblastoma multiforme mesenchymal subtype and independently predicts poor prognosis. Int J Mol Sci. 2019; 20: 6355.
Pan YB, Zhang CH, Wang SQ, Ai PH, Chen K, Zhu L, et al. Transforming growth factor beta induced (TGFBI) is a potential signature gene for mesenchymal subtype high-grade glioma. J Neurooncol. 2018; 137: 395-407.
Wu L, Chai R, Lin Z, Wu R, Yao D, Jiang T, et al. Evolution-driven crosstalk between glioblastoma and the tumor microenvironment. Cancer Biol Med. 2023; 20: 319-24.
Li H, He J, Li M, Li K, Pu X, Guo Y. Immune landscape-based machine-learning-assisted subclassification, prognosis, and immunotherapy prediction for glioblastoma. Front Immunol. 2022; 13: 1027631.
Martinez-Lage M, Lynch TM, Bi Y, Cocito C, Way GP, Pal S, et al. Immune landscapes associated with different glioblastoma molecular subtypes. Acta Neuropathol Commun. 2019; 7: 203.
Kaffes I, Szulzewsky F, Chen Z, Herting CJ, Gabanic B, Velazquez Vega JE, et al. Human Mesenchymal glioblastomas are characterized by an increased immune cell presence compared to Proneural and Classical tumors. Oncoimmunology. 2019; 8: e1655360.
Jeanmougin M, Havik AB, Cekaite L, Brandal P, Sveen A, Meling TR, et al. Improved prognostication of glioblastoma beyond molecular subtyping by transcriptional profiling of the tumor microenvironment. Mol Oncol. 2020; 14: 1016-27.
Sa JK, Chang N, Lee HW, Cho HJ, Ceccarelli M, Cerulo L, et al. Transcriptional regulatory networks of tumor-associated macrophages that drive malignancy in mesenchymal glioblastoma. Genome Biol. 2020; 21: 216.
Akkari L, Bowman RL, Tessier J, Klemm F, Handgraaf SM, de Groot M, et al. Dynamic changes in glioma macrophage populations after radiotherapy reveal CSF-1R inhibition as a strategy to overcome resistance. Sci Transl Med. 2020; 12: eaaw7843.
Dumas AA, Pomella N, Rosser G, Guglielmi L, Vinel C, Millner TO, et al. Microglia promote glioblastoma via mTOR-mediated immunosuppression of the tumour microenvironment. EMBO J. 2020; 39: e103790.
Agnihotri S, Zadeh G. Metabolic reprogramming in glioblastoma: the influence of cancer metabolism on epigenetics and unanswered questions. Neuro Oncol. 2016; 18: 160-72.
Mao P, Joshi K, Li J, Kim SH, Li P, Santana-Santos L, et al. Mesenchymal glioma stem cells are maintained by activated glycolytic metabolism involving aldehyde dehydrogenase 1A3. Proc Natl Acad Sci U S A. 2013; 110: 8644-9.
Vegran F, Boidot R, Michiels C, Sonveaux P, Feron O. Lactate influx through the endothelial cell monocarboxylate transporter MCT1 supports an NF-kappaB/IL-8 pathway that drives tumor angiogenesis. Cancer Res. 2011; 71: 2550-60.
Kennedy KM, Dewhirst MW. Tumor metabolism of lactate: the influence and therapeutic potential for MCT and CD147 regulation. Future Oncol. 2010; 6: 127-48.
Heiland DH, Worner J, Gerrit Haaker J, Delev D, Pompe N, Mercas B, et al. The integrative metabolomic-transcriptomic landscape of glioblastome multiforme. Oncotarget. 2017; 8: 49178-90.
Oizel K, Chauvin C, Oliver L, Gratas C, Geraldo F, Jarry U, et al. Efficient mitochondrial glutamine targeting prevails over glioblastoma metabolic plasticity. Clin Cancer Res. 2017; 23: 6292-304.
Wang LB, Karpova A, Gritsenko MA, Kyle JE, Cao S, Li Y, et al. Proteogenomic and metabolomic characterization of human glioblastoma. Cancer Cell. 2021; 39: 509-28.
Pieri V, Gallotti AL, Drago D, Cominelli M, Pagano I, Conti V, et al. Aberrant L-fucose accumulation and increased core fucosylation are metabolic liabilities in mesenchymal glioblastoma. Cancer Res. 2023; 83: 195-218.
Puchalski RB, Shah N, Miller J, Dalley R, Nomura SR, Yoon JG, et al. An anatomic transcriptional atlas of human glioblastoma. Science. 2018; 360: 660-3.
Minata M, Audia A, Shi J, Lu S, Bernstock J, Pavlyukov MS, et al. Phenotypic plasticity of invasive edge glioma stem-like cells in response to ionizing radiation. Cell Rep. 2019; 26: 1893-905.
Gill BJ, Pisapia DJ, Malone HR, Goldstein H, Lei L, Sonabend A, et al. MRI-localized biopsies reveal subtype-specific differences in molecular and cellular composition at the margins of glioblastoma. Proc Natl Acad Sci U S A. 2014; 111: 12550-5.
Kvisten M, Mikkelsen VE, Stensjoen AL, Solheim O, Van Der Want J, Torp SH. Microglia and macrophages in human glioblastomas: a morphological and immunohistochemical study. Mol Clin Oncol. 2019; 11: 31-6.
Lathia JD, Mack SC, Mulkearns-Hubert EE, Valentim CL, Rich JN. Cancer stem cells in glioblastoma. Genes Dev. 2015; 29: 1203-17.
Halliday J, Helmy K, Pattwell SS, Pitter KL, LaPlant Q, Ozawa T, et al. In vivo radiation response of proneural glioma characterized by protective p53 transcriptional program and proneural-mesenchymal shift. Proc Natl Acad Sci U S A. 2014; 111: 5248-53.
Spinelli C, Montermini L, Meehan B, Brisson AR, Tan S, Choi D, et al. Molecular subtypes and differentiation programmes of glioma stem cells as determinants of extracellular vesicle profiles and endothelial cell-stimulating activities. J Extracell Vesicles. 2018; 7: 1490144.
Lottaz C, Beier D, Meyer K, Kumar P, Hermann A, Schwarz J, et al. Transcriptional profiles of CD133+ and CD133- glioblastoma-derived cancer stem cell lines suggest different cells of origin. Cancer Res. 2010; 70: 2030-40.
Marziali G, Signore M, Buccarelli M, Grande S, Palma A, Biffoni M, et al. Metabolic/proteomic signature defines two glioblastoma subtypes with different clinical outcome. Sci Rep. 2016; 6: 21557.
Brown DV, Daniel PM, D’Abaco GM, Gogos A, Ng W, Morokoff AP, et al. Coexpression analysis of CD133 and CD44 identifies proneural and mesenchymal subtypes of glioblastoma multiforme. Oncotarget. 2015; 6: 6267-80.
Garnier D, Renoult O, Alves-Guerra MC, Paris F, Pecqueur C. Glioblastoma stem-like cells, metabolic strategy to kill a challenging target. Front Oncol. 2019; 9: 118.
Steponaitis G, Tamasauskas A. Mesenchymal and proneural subtypes of glioblastoma disclose branching based on GSC associated signature. Int J Mol Sci. 2021; 22: 4964.
Richards LM, Whitley OKN, MacLeod G, Cavalli FMG, Coutinho FJ, Jaramillo JE, et al. Gradient of Developmental and Injury Response transcriptional states defines functional vulnerabilities underpinning glioblastoma heterogeneity. Nat Cancer. 2021; 2: 157-73.
Wang J, Cazzato E, Ladewig E, Frattini V, Rosenbloom DI, Zairis S, et al. Clonal evolution of glioblastoma under therapy. Nat Genet. 2016; 48: 768-76.
Sikdar S, Datta S. A novel statistical approach for identification of the master regulator transcription factor. BMC Bioinformatics. 2017; 18: 79.
Carro MS, Lim WK, Alvarez MJ, Bollo RJ, Zhao X, Snyder EY, et al. The transcriptional network for mesenchymal transformation of brain tumours. Nature. 2010; 463: 318-25.
Bhat KP, Salazar KL, Balasubramaniyan V, Wani K, Heathcock L, Hollingsworth F, et al. The transcriptional coactivator TAZ regulates mesenchymal differentiation in malignant glioma. Genes Dev. 2011; 25: 2594-609.
Yee PP, Wei Y, Kim SY, Lu T, Chih SY, Lawson C, et al. Neutrophil-induced ferroptosis promotes tumor necrosis in glioblastoma progression. Nat Commun. 2020; 11: 5424.
Yamini B. NF-kappaB, mesenchymal differentiation and glioblastoma. Cells. 2018; 7: 125.
Fedele M, Cerchia L, Pegoraro S, Sgarra R, Manfioletti G. Proneural-mesenchymal transition: phenotypic plasticity to acquire multitherapy resistance in glioblastoma. Int J Mol Sci. 2019; 20: 2746.
Chow KH, Park HJ, George J, Yamamoto K, Gallup AD, Graber JH, et al. S100A4 is a biomarker and regulator of glioma stem cells that is critical for mesenchymal transition in glioblastoma. Cancer Res. 2017; 77: 5360-73.
Marques C, Unterkircher T, Kroon P, Oldrini B, Izzo A, Dramaretska Y, et al. NF1 regulates mesenchymal glioblastoma plasticity and aggressiveness through the AP-1 transcription factor FOSL1. Elife. 2021; 10: e64846.
Cheng P, Wang J, Waghmare I, Sartini S, Coviello V, Zhang Z, et al. FOXD1-ALDH1A3 signaling is a determinant for the self-renewal and tumorigenicity of mesenchymal glioma stem cells. Cancer Res. 2016; 76: 7219-30.
Zhang Q, Chen Z, Tang Q, Wang Z, Lu J, You Y, et al. USP21 promotes self-renewal and tumorigenicity of mesenchymal glioblastoma stem cells by deubiquitinating and stabilizing FOXD1. Cell Death Dis. 2022; 13: 712.
Chen Z, Wang HW, Wang S, Fan L, Feng S, Cai X, et al. USP9X deubiquitinates ALDH1A3 and maintains mesenchymal identity in glioblastoma stem cells. J Clin Invest. 2019; 129: 2043-55.
Fan L, Chen Z, Wu X, Cai X, Feng S, Lu J, et al. Ubiquitin-specific protease 3 promotes glioblastoma cell invasion and epithelial-mesenchymal transition via stabilizing snail. Mol Cancer Res. 2019; 17: 1975-84.
Qiu W, Cai X, Xu K, Song S, Xiao Z, Hou Y, et al. PRL1 promotes glioblastoma invasion and tumorigenesis via activating USP36-mediated Snail2 deubiquitination. Front Oncol. 2021; 11: 795633.
Huang P, Guo Y, Zhao Z, Ning W, Wang H, Gu C, et al. UBE2T promotes glioblastoma invasion and migration via stabilizing GRP78 and regulating EMT. Aging (Albany NY). 2020; 12: 10275-89.
Zhang C, Han X, Xu X, Zhou Z, Chen X, Tang Y, et al. FoxM1 drives ADAM17/EGFR activation loop to promote mesenchymal transition in glioblastoma. Cell Death Dis. 2018; 9: 469.
Chong YK, Sandanaraj E, Koh LW, Thangaveloo M, Tan MS, Koh GR, et al. ST3GAL1-associated transcriptomic program in glioblastoma tumor growth, invasion, and prognosis. J Natl Cancer Inst. 2016; 108: djv326.
Xue BZ, Xiang W, Zhang Q, Wang HF, Zhou YJ, Tian H, et al. CD90(low) glioma-associated mesenchymal stromal/stem cells promote temozolomide resistance by activating FOXS1-mediated epithelial-mesenchymal transition in glioma cells. Stem Cell Res Ther. 2021; 12: 394.
Sha Z, Zhou J, Wu Y, Zhang T, Li C, Meng Q, et al. BYSL promotes glioblastoma cell migration, invasion, and mesenchymal transition through the GSK-3β/β-catenin signaling pathway. Front Oncol. 2020; 10: 565225.
Yang W, Wu PF, Ma JX, Liao MJ, Wang XH, Xu LS, et al. Sortilin promotes glioblastoma invasion and mesenchymal transition through GSK-3β/β-catenin/twist pathway. Cell Death Dis. 2019; 10: 208.
Polonen P, Jawahar Deen A, Leinonen HM, Jyrkkanen HK, Kuosmanen S, Mononen M, et al. Nrf2 and SQSTM1/p62 jointly contribute to mesenchymal transition and invasion in glioblastoma. Oncogene. 2019; 38: 7473-90.
Zhang G, Tanaka S, Jiapaer S, Sabit H, Tamai S, Kinoshita M, et al. RBPJ contributes to the malignancy of glioblastoma and induction of proneural-mesenchymal transition via IL-6-STAT3 pathway. Cancer Sci. 2020; 111: 4166-76.
Chesnelong C, Hao X, Cseh O, Wang AY, Luchman HA, Weiss S. SLUG directs the precursor state of human brain tumor stem cells. Cancers (Basel). 2019; 11: 1635.
Ma YS, Wu ZJ, Bai RZ, Dong H, Xie BX, Wu XH, et al. DRR1 promotes glioblastoma cell invasion and epithelial-mesenchymal transition via regulating AKT activation. Cancer Lett. 2018; 423: 86-94.
Natesh K, Bhosale D, Desai A, Chandrika G, Pujari R, Jagtap J, et al. Oncostatin-M differentially regulates mesenchymal and proneural signature genes in gliomas via STAT3 signaling. Neoplasia. 2015; 17: 225-37.
Xu X, Bao Z, Liu Y, Jiang K, Zhi T, Wang D, et al. PBX3/MEK/ERK1/2/LIN28/let-7b positive feedback loop enhances mesenchymal phenotype to promote glioblastoma migration and invasion. J Exp Clin Cancer Res. 2018; 37: 158.
Yang J, Wu X, Wang J, Guo X, Chen J, Yang X, et al. Feedforward loop between IMP1 and YAP/TAZ promotes tumorigenesis and malignant progression in glioblastoma. Cancer Sci. 2022; 114: 2053-62.
Tang H, Zhao J, Zhang L, Zhao J, Zhuang Y, Liang P. SRPX2 Enhances the epithelial-mesenchymal transition and temozolomide resistance in glioblastoma cells. Cell Mol Neurobiol. 2016; 36: 1067-76.
Sun H, Long S, Wu B, Liu J, Li G. NKCC1 involvement in the epithelial-to-mesenchymal transition is a prognostic biomarker in gliomas. PeerJ. 2020; 8: e8787.
Zuchegna C, Di Zazzo E, Moncharmont B, Messina S. Dual-specificity phosphatase (DUSP6) in human glioblastoma: epithelial-to-mesenchymal transition (EMT) involvement. BMC Res Notes. 2020; 13: 374.
Hernandez-Vega AM, Del Moral-Morales A, Zamora-Sanchez CJ, Pina-Medina AG, Gonzalez-Arenas A, Camacho-Arroyo I. Estradiol induces epithelial to mesenchymal transition of human glioblastoma cells. Cells. 2020; 9: 1930.
Li CW, Xia W, Huo L, Lim SO, Wu Y, Hsu JL, et al. Epithelial-mesenchymal transition induced by TNF-alpha requires NF-kappaB-mediated transcriptional upregulation of Twist1. Cancer Res. 2012; 72: 1290-300.
Mikheeva SA, Mikheev AM, Petit A, Beyer R, Oxford RG, Khorasani L, et al. TWIST1 promotes invasion through mesenchymal change in human glioblastoma. Mol Cancer. 2010; 9: 194.
De Craene B, Berx G. Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer. 2013; 13: 97-110.
Angel I, Pilo Kerman O, Rousso-Noori L, Friedmann-Morvinski D. Tenascin C promotes cancer cell plasticity in mesenchymal glioblastoma. Oncogene. 2020; 39: 6990-7004.
Wang Z, Shi Y, Ying C, Jiang Y, Hu J. Hypoxia-induced PLOD1 overexpression contributes to the malignant phenotype of glioblastoma via NF-kappaB signaling. Oncogene. 2021; 40: 1458-75.
Alafate W, Li X, Zuo J, Zhang H, Xiang J, Wu W, et al. Elevation of CXCL1 indicates poor prognosis and radioresistance by inducing mesenchymal transition in glioblastoma. CNS Neurosci Ther. 2020; 26: 475-85.
Lou JC, Lan YL, Gao JX, Ma BB, Yang T, Yuan ZB, et al. Silencing NUDT21 attenuates the mesenchymal identity of glioblastoma cells via the NF-kappaB pathway. Front Mol Neurosci. 2017; 10: 420.
Gao Z, Xu J, Fan Y, Zhang Z, Wang H, Qian M, et al. ARPC1B promotes mesenchymal phenotype maintenance and radiotherapy resistance by blocking TRIM21-mediated degradation of IFI16 and HuR in glioma stem cells. J Exp Clin Cancer Res. 2022; 41: 323.
Wu J, Shen S, Liu T, Ren X, Zhu C, Liang Q, et al. Chemerin enhances mesenchymal features of glioblastoma by establishing autocrine and paracrine networks in a CMKLR1-dependent manner. Oncogene. 2022; 41: 3024-36.
Liang Y, Voshart D, Paridaen J, Oosterhof N, Liang D, Thiruvalluvan A, et al. CD146 increases stemness and aggressiveness in glioblastoma and activates YAP signaling. Cell Mol Life Sci. 2022; 79: 398.
Kim SH, Ezhilarasan R, Phillips E, Gallego-Perez D, Sparks A, Taylor D, et al. Serine/threonine kinase MLK4 determines mesenchymal identity in glioma stem cells in an NF-kappaB-dependent manner. Cancer Cell. 2016; 29: 201-13.
Li S, Jiang X, Guan M, Zhang Y, Cao Y, Zhang L. The overexpression of GPX8 is correlated with poor prognosis in GBM patients. Front Genet. 2022; 13: 898204.
Yan T, Tan Y, Deng G, Sun Z, Liu B, Wang Y, et al. TGF-beta induces GBM mesenchymal transition through upregulation of CLDN4 and nuclear translocation to activate TNF-alpha/NF-kappaB signal pathway. Cell Death Dis. 2022; 13: 339.
Yin J, Oh YT, Kim JY, Kim SS, Choi E, Kim TH, et al. Transglutaminase 2 inhibition reverses mesenchymal transdifferentiation of glioma stem cells by regulating C/EBPbeta signaling. Cancer Res. 2017; 77: 4973-84.
Lv SQ, Fu Z, Yang L, Li QR, Zhu J, Gai QJ, et al. Comprehensive omics analyses profile genesets related with tumor heterogeneity of multifocal glioblastomas and reveal LIF/CCL2 as biomarkers for mesenchymal subtype. Theranostics. 2022; 12: 459-73.
Li G, Li Y, Liu X, Wang Z, Zhang C, Wu F, et al. ALDH1A3 induces mesenchymal differentiation and serves as a predictor for survival in glioblastoma. Cell Death Dis. 2018; 9: 1190.
Song Y, Jiang Y, Tao D, Wang Z, Wang R, Wang M, et al. NFAT2-HDAC1 signaling contributes to the malignant phenotype of glioblastoma. Neuro Oncol. 2020; 22: 46-57.
Yang M, Chen X, Zhang J, Xiong E, Wang Q, Fang W, et al. ME2 promotes proneural-mesenchymal transition and lipogenesis in glioblastoma. Front Oncol. 2021; 11: 715593.
Lin Z, Zhang Z, Zheng H, Xu H, Wang Y, Chen C, et al. Molecular mechanism by which CDCP1 promotes proneural-mesenchymal transformation in primary glioblastoma. Cancer Cell Int. 2022; 22: 151.
Yachi K, Tsuda M, Kohsaka S, Wang L, Oda Y, Tanikawa S, et al. miR-23a promotes invasion of glioblastoma via HOXD10-regulated glial-mesenchymal transition. Signal Transduct Target Ther. 2018; 3: 33.
Liu Q, Guan Y, Li Z, Wang Y, Liu Y, Cui R, et al. miR-504 suppresses mesenchymal phenotype of glioblastoma by directly targeting the FZD7-mediated Wnt-beta-catenin pathway. J Exp Clin Cancer Res. 2019; 38: 358.
Huang T, Alvarez AA, Pangeni RP, Horbinski CM, Lu S, Kim SH, et al. A regulatory circuit of miR-125b/miR-20b and Wnt signalling controls glioblastoma phenotypes through FZD6-modulated pathways. Nat Commun. 2016; 7: 12885.
Xu R, Zhou F, Yu T, Xu G, Zhang J, Wang Y, et al. MicroRNA-940 inhibits epithelial-mesenchymal transition of glioma cells via targeting ZEB2. Am J Transl Res. 2019; 11: 7351-63.
Chen W, Kong KK, Xu XK, Chen C, Li H, Wang FY, et al. Downregulation of miR-205 is associated with glioblastoma cell migration, invasion, and the epithelial-mesenchymal transition, by targeting ZEB1 via the Akt/mTOR signaling pathway. Int J Oncol. 2018; 52: 485-95.
Chen W, Huang B, Wang E, Wang X. MiR-145 inhibits EGF-induced epithelial-to-mesenchymal transition via targeting Smad2 in human glioblastoma. Onco Targets Ther. 2019; 12: 3099-107.
Li Z, Qian R, Zhang J, Shi X. MiR-218-5p targets LHFPL3 to regulate proliferation, migration, and epithelial-mesenchymal transitions of human glioma cells. Biosci Rep. 2019; 39: BSR20180879.
Wang X, Wang E, Cao J, Xiong F, Yang Y, Liu H. MiR-145 inhibits the epithelial-to-mesenchymal transition via targeting ADAM19 in human glioblastoma. Oncotarget. 2017; 8: 92545-54.
Ma C, Wei F, Xia H, Liu H, Dong X, Zhang Y, et al. MicroRNA-10b mediates TGF-beta1-regulated glioblastoma proliferation, migration and epithelial-mesenchymal transition. Int J Oncol. 2017; 50: 1739-48.
He X, Liu Z, Peng Y, Yu C. MicroRNA-181c inhibits glioblastoma cell invasion, migration and mesenchymal transition by targeting TGF-beta pathway. Biochem Biophys Res Commun. 2016; 469: 1041-8.
Yang F, Liu X, Liu Y, Liu Y, Zhang C, Wang Z, et al. miR-181d/MALT1 regulatory axis attenuates mesenchymal phenotype through NF-kappaB pathways in glioblastoma. Cancer Lett. 2017; 396: 1-9.
Wang W, Hao Y, Zhang A, Yang W, Wei W, Wang G, et al. miR-19a/b promote EMT and proliferation in glioma cells via SEPT7-AKT-NF-kappaB pathway. Mol Ther Oncolytics. 2021; 20: 290-305.
Bier A, Hong X, Cazacu S, Goldstein H, Rand D, Xiang C, et al. miR-504 modulates the stemness and mesenchymal transition of glioma stem cells and their interaction with microglia via delivery by extracellular vesicles. Cell Death Dis. 2020; 11: 899.
Gao Z, Xu J, Fan Y, Qi Y, Wang S, Zhao S, et al. PDIA3P1 promotes Temozolomide resistance in glioblastoma by inhibiting C/EBPbeta degradation to facilitate proneural-to-mesenchymal transition. J Exp Clin Cancer Res. 2022; 41: 223.
Tang G, Luo L, Zhang J, Zhai D, Huang D, Yin J, et al. lncRNA LINC01057 promotes mesenchymal differentiation by activating NF-kappaB signaling in glioblastoma. Cancer Lett. 2021; 498: 152-64.
Xu C, Zhao J, Song J, Xiao M, Cui X, Xin L, et al. lncRNA PRADX is a mesenchymal glioblastoma biomarker for cellular metabolism targeted therapy. Front Oncol. 2022; 12: 888922.
Cai J, Zhang J, Wu P, Yang W, Ye Q, Chen Q, et al. Blocking LINC00152 suppresses glioblastoma malignancy by impairing mesenchymal phenotype through the miR-612/AKT2/NF-kappaB pathway. J Neurooncol. 2018; 140: 225-36.
Li C, Zheng H, Hou W, Bao H, Xiong J, Che W, et al. Long non-coding RNA linc00645 promotes TGF-beta-induced epithelial-mesenchymal transition by regulating miR-205-3p-ZEB1 axis in glioma. Cell Death Dis. 2019; 10: 717.
Shree B, Tripathi S, Sharma V. Transforming growth factor-Beta-regulated LncRNA-MUF promotes Invasion by modulating the miR-34a Snail1 Axis in Glioblastoma Multiforme. Front Oncol. 2021; 11: 788755.
Dong N, Guo J, Han S, Bao L, Diao Y, Lin Z. Positive feedback loop of lncRNA HOXC-AS2/miR-876-5p/ZEB1 to regulate EMT in glioma. Onco Targets Ther. 2019; 12: 7601-9.
Brodie S, Lee HK, Jiang W, Cazacu S, Xiang C, Poisson LM, et al. The novel long non-coding RNA TALNEC2, regulates tumor cell growth and the stemness and radiation response of glioma stem cells. Oncotarget. 2017; 8: 31785-801.
Wang H, Li L, Yin L. Silencing LncRNA LOXL1-AS1 attenuates mesenchymal characteristics of glioblastoma via NF-kappaB pathway. Biochem Biophys Res Commun. 2018; 500: 518-24.
Yin T, Wu J, Hu Y, Zhang M, He J. Long non-coding RNA HULC stimulates the epithelial-mesenchymal transition process and vasculogenic mimicry in human glioblastoma. Cancer Med. 2021; 10: 5270-82.
Zhu H, Chen Z, Shen L, Tang T, Yang M, Zheng X. Long noncoding RNA LINC-PINT suppresses cell proliferation, invasion, and EMT by blocking Wnt/beta-catenin signaling in glioblastoma. Front Pharmacol. 2020; 11: 586653.
Chen WL, Jiang L, Wang JS, Liao CX. Circ-0001801 contributes to cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT) in glioblastoma by regulating miR-628-5p/HMGB3 axis. Eur Rev Med Pharmacol Sci. 2019; 23: 10874-85.
Zhou F, Wang B, Wang H, Hu L, Zhang J, Yu T, et al. circMELK promotes glioblastoma multiforme cell tumorigenesis through the miR-593/EphB2 axis. Mol Ther Nucleic Acids. 2021; 25: 25-36.
Gupta K, Burns TC. Radiation-induced alterations in the recurrent glioblastoma microenvironment: therapeutic implications. Front Oncol. 2018; 8: 503.
Lau J, Ilkhanizadeh S, Wang S, Miroshnikova YA, Salvatierra NA, Wong RA, et al. STAT3 blockade inhibits radiation-induced malignant progression in glioma. Cancer Res. 2015; 75: 4302-11.
Kesanakurti D, Maddirela D, Banasavadi-Siddegowda YK, Lai TH, Qamri Z, Jacob NK, et al. A novel interaction of PAK4 with PPARgamma to regulate Nox1 and radiation-induced epithelial-to-mesenchymal transition in glioma. Oncogene. 2017; 36: 5309-20.
Yoo KC, Kang JH, Choi MY, Suh Y, Zhao Y, Kim MJ, et al. Soluble ICAM-1 a pivotal communicator between tumors and macrophages, promotes mesenchymal shift of glioblastoma. Adv Sci (Weinh). 2022; 9: e2102768.
Li Y, Ren Z, Peng Y, Li K, Wang X, Huang G, et al. Classification of glioma based on prognostic alternative splicing. BMC Med Genomics. 2019; 12: 165.
Li Y, Wang X, Qi S, Gao L, Huang G, Ren Z, et al. Spliceosome-regulated RSRP1-dependent NF-kappaB activation promotes the glioblastoma mesenchymal phenotype. Neuro Oncol. 2021; 23: 1693-708.
Zanotto-Filho A, Goncalves RM, Klafke K, de Souza PO, Dillenburg FC, Carro L, et al. Inflammatory landscape of human brain tumors reveals an NFkappaB dependent cytokine pathway associated with mesenchymal glioblastoma. Cancer Lett. 2017; 390: 176-87.
Yi L, Tong L, Li T, Hai L, Abeysekera IR, Tao Z, et al. Bioinformatic analyses reveal the key pathways and genes in the CXCR4 mediated mesenchymal subtype of glioblastoma. Mol Med Rep. 2018; 18: 741-8.
Khan AB, Lee S, Harmanci AS, Patel R, Latha K, Yang Y, et al. CXCR4 expression is associated with proneural-to-mesenchymal transition in glioblastoma. Int J Cancer. 2023; 152: 713-24.
Piao Y, Liang J, Holmes L, Henry V, Sulman E, de Groot JF. Acquired resistance to anti-VEGF therapy in glioblastoma is associated with a mesenchymal transition. Clin Cancer Res. 2013; 19: 4392-403.
Huang M, Zhang D, Wu JY, Xing K, Yeo E, Li C, et al. Wnt-mediated endothelial transformation into mesenchymal stem cell-like cells induces chemoresistance in glioblastoma. Sci Transl Med. 2020; 12: eaay7522.
Liu T, Ma W, Xu H, Huang M, Zhang D, He Z, et al. PDGF-mediated mesenchymal transformation renders endothelial resistance to anti-VEGF treatment in glioblastoma. Nat Commun. 2018; 9: 3439.
Adnani L, Kassouf J, Meehan B, Spinelli C, Tawil N, Nakano I, et al. Angiocrine extracellular vesicles impose mesenchymal reprogramming upon proneural glioma stem cells. Nat Commun. 2022; 13: 5494.
Schweiger MW, Li M, Giovanazzi A, Fleming RL, Tabet EI, Nakano I, et al. Extracellular vesicles induce mesenchymal transition and therapeutic resistance in glioblastomas through NF-kappaB/STAT3 signaling. Adv Biosyst. 2020; 4: e1900312.
Zhang Z, Xu J, Chen Z, Wang H, Xue H, Yang C, et al. Transfer of MicroRNA via macrophage-derived extracellular vesicles promotes proneural-to-mesenchymal transition in glioma stem cells. Cancer Immunol Res. 2020; 8: 966-81.
Monteiro AR, Hill R, Pilkington GJ, Madureira PA. The role of hypoxia in glioblastoma invasion. Cells. 2017; 6: 45.
Joseph JV, Conroy S, Pavlov K, Sontakke P, Tomar T, Eggens-Meijer E, et al. Hypoxia enhances migration and invasion in glioblastoma by promoting a mesenchymal shift mediated by the HIF1alpha-ZEB1 axis. Cancer Lett. 2015; 359: 107-16.
Qiu W, Song S, Chen W, Zhang J, Yang H, Chen Y. Hypoxia-induced EPHB2 promotes invasive potential of glioblastoma. Int J Clin Exp Pathol. 2019; 12: 539-48.
Batchelor TT, Sorensen AG, di Tomaso E, Zhang WT, Duda DG, Cohen KS, et al. AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell. 2007; 11: 83-95.
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016; 131: 803-20.
Creative Commons Attribution-NonCommercial 4.0 International License
京公网安备11010802044758号