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
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Genes & Diseases Article
PDF (497.6 KB)
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Review Article | Open Access

The Role and Function of Ras-association domain family in Cancer: A Review

Mohammad Reza Zinatizadeha,b,1( ), Seyed Ali Momenic,1, Peyman Kheirandish Zarandia,b, Ghanbar Mahmoodi Chalbatanib, Hassan Danab, Hamid Reza Mirzaeid, Mohammad Esmaeil Akbaria, Seyed Rouhollah Mirib
Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Science, Tehran, Iran
Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, IR, Iran
Cancer Research Center, Shohadae Tajrish Hospital, Department of Radiation Oncology, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Peer review under responsibility of Chongqing Medical University.

1 These authors contributed equally to this work.

Show Author Information

Abstract

Ras gene mutation has been observed in more than 30% of cancers, and 90% of pancreatic, lung and colon cancers. Ras proteins (K-Ras, H-Ras, N-Ras) act as molecular switches which are activated by binding to GTP. They play a role in the cascade of cell process control (proliferation and cell division). In the inactive state, transforming GTP to GDP leads to the activation of GTpase in Ras gene. However, the mutation in Ras leads to the loss of internal GTPase activity and permanent activation of the protein. The activated Ras can promote the cell death or stop cell growth, which are facilitated by Ras-association domain family. Various studies have been conducted to determine the importance of losing RASSF proteins in Ras-induced tumors. This paper examines the role of Ras and RASSF proteins. In general, RASSF proteins can be used as a suitable means for targeting a large group of Ras-induced tumors.

Keywords

CancerLungColonH-RasK-RasN-RasPancreatic

References

1
Azmi Asfar. Conquering RAS: From Biology to Cancer Therapy. Elsevier; 2016.
2

Zinatizadeh MR, Masoumalinejad Z, Parnak F. Prevalence of Mycoplasma hyorhinis contamination in tissues samples from cancer patients: a Brief Report. Mod Med Lab J. 2017;1(3):91-95.
Crossref Google Scholar
3

Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer. 2003;3(1):11-22.
Crossref Google Scholar
4

Donninger H, Vos MD, Clark GJ. The RASSF1A tumor suppressor. J Cell Sci. 2007;120(18):3163-3172.
Crossref Google Scholar
5

Overmeyer JH, Maltese WA. Death pathways triggered by activated Ras in cancer cells. Front Biosci. 2011;16(5):1693-1713.
Crossref Google Scholar
6

Kim DH, Kim JS, Park JH, et al. Relationship of Ras association domain family 1 methylation and K-ras mutation in primary non-small cell lung cancer. Cancer Res. 2003;63(19):6206-6211.
Google Scholar
7

Calvisi DF, Ladu S, Gorden A, et al. Ubiquitous activation of Ras and Jak/Stat pathways in human HCC. Gastroenterology. 2006;130(4):1117-1128.
Crossref Google Scholar
8

Fukatsu A, Ishiguro F, Tanaka I, et al. RASSF3 downregulation increases malignant phenotypes of non-small cell lung cancer. Lung Cancer. 2014;83(1):23-29.
Crossref Google Scholar
9

Mezzanotte JJ, Hill VC, Schmidt ML, et al. RASSF6 exhibits promoter hypermethylation in metastatic melanoma and inhibits invasion in melanoma cells. Epigenetics. 2014;9(11):1496-1503.
Crossref Google Scholar
10

Hamilton G, Yee KS, Scarce S, O'Neill E. ATM regulates a RASSF1A-dependent DNA damage response. Curr Biol. 2009;19(23):2020-2025.
Crossref Google Scholar
11

Cox AD, Fesik SW, Kimmelman AC, Luo J, Der CJ. Drugging the undruggable RAS: mission possible? Nat Rev Drug Discov. 2014;13(11):828-851.
Crossref Google Scholar
12

Guo C, Tommasi S, Liu L, Yee JK, Dammann R, Pfeifer GP. RASSF1A is part of a complex similar to the Drosophila Hippo/Salvador/Lats tumor-suppressor network. Curr Biol. 2007;17(8):700-705.
Crossref Google Scholar
13

Khokhlatchev A, Rabizadeh S, Xavier R, et al. Identification of a novel Ras-regulated proapoptotic pathway. Curr Biol. 2002;12(4):253-265.
Crossref Google Scholar
14

Donninger H, Calvisi DF, Barnoud T, et al. NORE1A is a Ras senescence effector that controls the apoptotic/senescent balance of p53 via HIPK2. J Cell Biol. 2015;208(6):777-789.
Crossref Google Scholar
15

Matallanas D, Romano D, Yee K, et al. RASSF1A elicits apoptosis through an MST2 pathway directing proapoptotic transcription by the p73 tumor suppressor protein. Mol Cell. 2007;27(6):962-975.
Crossref Google Scholar
16

Vos MD, Ellis CA, Bell A, Birrer MJ, Clark GJ. Ras uses the novel tumor suppressor RASSF1 as an effector to mediate apoptosis. J Biol Chem. 2000;275(46):35669-35672.
Crossref Google Scholar
17

Ortiz-Vega S, Khokhlatchev A, Nedwidek M, et al. The putative tumor suppressor RASSF1A homodimerizes and heterodimerizes with the Ras-GTP binding protein Nore1. Oncogene. 2002;21(9):1381-1390.
Crossref Google Scholar
18

Land H, Parada LF, Weinberg RA. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983;304(5927):596-602.
Crossref Google Scholar
19

Shivakumar L, Minna J, Sakamaki T, Pestell R, White MA. The RASSF1A tumor suppressor blocks cell cycle progression and inhibits cyclin D1 accumulation. Mol Cell Biol. 2002;22(12):4309-4318.
Crossref Google Scholar
20

Dallol A, Agathanggelou A, Fenton SL, et al. RASSF1A interacts with microtubule-associated proteins and modulates microtubule dynamics. Cancer Res. 2004;64(12):4112-4116.
Crossref Google Scholar
21

Vos MD, Martinez A, Elam C, et al. A role for the RASSF1A tumor suppressor in the regulation of tubulin polymerization and genomic stability. Cancer Res. 2004;64(12):4244-4250.
Crossref Google Scholar
22

Arnette C, Efimova N, Zhu X, Clark GJ, Kaverina I. Microtubule segment stabilization by RASSF1A is required for proper microtubule dynamics and Golgi integrity. Mol Biol Cell. 2014;25(6):800-810.
Crossref Google Scholar
23

Liu L, Vo A, Liu G, McKeehan WL. Distinct structural domains within C19ORF5 support association with stabilized microtubules and mitochondrial aggregation and genome destruction. Cancer Res. 2005;65(10):4191-4201.
Crossref Google Scholar
24

Baksh S, Tommasi S, Fenton S, et al. The tumor suppressor RASSF1A and MAP-1 link death receptor signaling to Bax conformational change and cell death. Mol Cell. 2005;18(6):637-650.
Crossref Google Scholar
25

Vos MD, Dallol A, Eckfeld K, et al. The RASSF1A tumor suppressor activates Bax via MOAP-1. J Biol Chem. 2006;281(18):4557-4563.
Crossref Google Scholar
26

Praskova M, Khoklatchev A, Ortiz-Vega S, Avruch J. Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras. Biochem J. 2004;381(2):453-462.
Crossref Google Scholar
27

Pan D. The hippo signaling pathway in development and cancer. Dev Cell. 2010;19(4):491-505.
Crossref Google Scholar
28

Harvey KF, Zhang X, Thomas DM. The Hippo pathway and human cancer. Nat Rev Cancer. 2013;13(4):246-257.
Crossref Google Scholar
29

Del Re DP, Matsuda T, Zhai P, et al. Proapoptotic Rassf1A/Mst1 signaling in cardiac fibroblasts is protective against pressure overload in mice. J Clin Investig. 2010;120(10):3555-3567.
Crossref Google Scholar
30

Romano D, Matallanas D, Weitsman G, Preisinger C, Ng T, Kolch W. Proapoptotic kinase MST2 coordinates signaling crosstalk between RASSF1A, Raf-1, and Akt. Cancer Res. 2010;70(3):1195-1203.
Crossref Google Scholar
31

Song MS, Song SJ, Kim SY, Oh HJ, Lim DS. The tumour suppressor RASSF1A promotes MDM2 self-ubiquitination by disrupting the MDM2-DAXX-HAUSP complex. EMBO J. 2008;27(13):1863-1874.
Crossref Google Scholar
32

Tommasi S, Besaratinia A, Wilczynski SP, Pfeifer GP. Loss of RASSF1A enhances p53-mediated tumor predisposition and accelerates progression to aneuploidy. Oncogene. 2011;30(6):690-700.
Crossref Google Scholar
33

Pefani DE, Latusek R, Pires I, et al. RASSF1A-LATS1 signalling stabilizes replication forks by restricting CDK2-mediated phosphorylation of BRCA2. Nat Cell Biol. 2014;16(10):962-971.
Crossref Google Scholar
34

Yee KS, Grochola L, Hamilton G, et al. A RASSF1A polymorphism restricts p53/p73 activation and associates with poor survival and accelerated age of onset of soft tissue sarcoma. Cancer Res. 2012;72(9):2206-2217.
Crossref Google Scholar
35

Donninger H, Clark J, Rinaldo F, et al. The RASSF1A tumor suppressor regulates XPA-mediated DNA repair. Mol Cell Biol. 2015;35(1):277-287.
Crossref Google Scholar
36

Gao B, Xie XJ, Huang C, et al. RASSF1A polymorphism A133S is associated with early onset breast cancer in BRCA1/2 mutation carriers. Cancer Res. 2008;68(1):22-25.
Crossref Google Scholar
37

Schagdarsurengin U, Seidel C, Ulbrich EJ, Kolbl H, Dittmer J, Dammann R. A polymorphism at codon 133 of the tumor suppressor RASSF1A is associated with tumorous alteration of the breast. Int J Oncol. 2005;27(1):185-191.
Crossref Google Scholar
38

Oceandy D, Pickard A, Prehar S, et al. Tumor suppressor Ras-association domain family 1 isoform A is a novel regulator of cardiac hypertrophy. Circulation. 2009;120(7):607-616.
Crossref Google Scholar
39

Jung HY, Jung JS, Whang YM, Kim YH. RASSF1A suppresses cell migration through inactivation of HDAC6 and increase of acetylated alpha-tubulin. Cancer Res Treat. 2013;45(2):134-144.
Crossref Google Scholar
40

Kouzarides T. Acetylation: a regulatory modification to rival phosphorylation? EMBO J. 2000;19(6):1176-1179.
Crossref Google Scholar
41

Tommasi S, Dammann R, Zhang Z, et al. Tumor susceptibility of RASSF1A knockout mice. Cancer Res. 2005;65(1):92-98.
Crossref Google Scholar
42

Ram RR, Mendiratta S, Bodemann BO, Torres MJ, Eskiocak U, White MA. RASSF1A inactivation unleashes a tumor suppressor/oncogene cascade with context-dependent consequences on cell cycle progression. Mol Cell Biol. 2014;34(12):2350-2358.
Crossref Google Scholar
43

Kitagawa D, Kajiho H, Negishi T, et al. Release of RASSF1C from the nucleus by Daxx degradation links DNA damage and SAPK/JNK activation. EMBO J. 2006;25(14):3286-3297.
Crossref Google Scholar
44

Lorenzato A, Martino C, Dani N, et al. The cellular apoptosis susceptibility CAS/CSE1L gene protects ovarian cancer cells from death by suppressing RASSF1C. FASEB J. 2012;26(6):2446-2456.
Crossref Google Scholar
45

Estrabaud E, Lassot I, Blot G, et al. RASSF1C, an isoform of the tumor suppressor RASSF1A, promotes the accumulation of beta-catenin by interacting with betaTrCP. Cancer Res. 2007;67(3):1054-1061.
Crossref Google Scholar
46

Vavvas D, Li X, Avruch J, Zhang XF. Identification of Nore1 as a potential ras effector. J Biol Chem. 1998;273(10):5439-5442.
Crossref Google Scholar
47

Wohlgemuth S, Kiel C, Kramer A, Serrano L, Wittinghofer F, Herrmann C. Recognizing and defining true Ras binding domains I: biochemical analysis. J Mol Biol. 2005;348(3):741-758.
Crossref Google Scholar
48

Kuznetsov S, Khokhlatchev AV. The growth and tumor suppressors NORE1A and RASSF1A are targets for calpain-mediated proteolysis. PLoS One. 2008;3(12):e3997.
Crossref Google Scholar
49

Chen J, Liu WO, Vos MD, et al. The t(1;3) breakpoint-spanning genes LSAMP and NORE1 are involved in clear cell renal cell carcinomas. Cancer Cell. 2003;4(5):405-413.
Crossref Google Scholar
50

Aoyama Y, Avruch J, Zhang XF. Nore1 inhibits tumor cell growth independent of Ras or the MST1/2 kinases. Oncogene. 2004;23(19):3426-3433.
Crossref Google Scholar
51

Calvisi DF, Donninger H, Vos MD, et al. NORE1A tumor suppressor candidate modulates p21CIP1 via p53. Cancer Res. 2009;69(11):4629-4637.
Crossref Google Scholar
52

Puca R, Nardinocchi L, Givol D, D'Orazi G. Regulation of p53 activity by HIPK2: molecular mechanisms and therapeutical implications in human cancer cells. Oncogene. 2010;29(31):4378-4387.
Crossref Google Scholar
53

Lee D, Park SJ, Sung KS, et al. MDM2 associates with Ras effector NORE1 to induce the degradation of oncoprotein HIPK1. EMBO Rep. 2012;13(2):163-169.
Crossref Google Scholar
54

Schmidt ML, Donninger H, Clark GJ. Ras regulates SCF(beta-TrCP) protein activity and specificity via its effector protein NORE1A. J Biol Chem. 2014;289(45):31102-31110.
Crossref Google Scholar
55

Orford K, Crockett C, Jensen JP, Weissman AM, Byers SW. Serine phosphorylation-regulated ubiquitination and degradation of beta-catenin. J Biol Chem. 1997;272(40):24735-24738.
Crossref Google Scholar
56

Park J, Kang SI, Lee SY, et al. Tumor suppressor ras association domain family 5 (RASSF5/NORE1) mediates death receptor ligand-induced apoptosis. J Biol Chem. 2010;285(45):35029-35038.
Crossref Google Scholar
57

Katagiri K, Ohnishi N, Kabashima K, et al. Crucial functions of the Rap1 effector molecule RAPL in lymphocyte and dendritic cell trafficking. Nat Immunol. 2004;5(10):1045-1051.
Crossref Google Scholar
58

Zhou D, Medoff BD, Chen L, et al. The Nore1B/Mst1 complex restrains antigen receptor-induced proliferation of naive T cells. Proc Natl Acad Sci USA. 2008;105(51):20321-20326.
Crossref Google Scholar
59

Ishiguro K, Avruch J, Landry A, et al. Nore1B regulates TCR signaling via ras and Carma1. Cell Signal. 2006;18(10):1647-1654.
Crossref Google Scholar
60

Miertzschke M, Stanley P, Bunney TD, Rodrigues-Lima F, Hogg N, Katan M. Characterization of interactions of adapter protein RAPL/Nore1B with RAP GTPases and their role in T cell migration. J Biol Chem. 2007;282(42):30629-30642.
Crossref Google Scholar
61

Macheiner D, Heller G, Kappel S, et al. NORE1B, a candidate tumor suppressor, is epigenetically silenced in human hepatocellular carcinoma. J Hepatol. 2006;45(1):81-89.
Crossref Google Scholar
62

Macheiner D, Gauglhofer C, Rodgarkia-Dara C, et al. NORE1B is a putative tumor suppressor in hepatocarcinogenesis and may act via RASSF1A. Cancer Res. 2009;69(1):235-242.
Crossref Google Scholar
63

Vos MD, Ellis CA, Elam C, Ulku AS, Taylor BJ, Clark GJ. RASSF2 is a novel K-Ras-specific effector and potential tumor suppressor. J Biol Chem. 2003;278(30):28045-28051.
Crossref Google Scholar
64

Akino K, Toyota M, Suzuki H, et al. The Ras effector RASSF2 is a novel tumor-suppressor gene in human colorectal cancer. Gastroenterology. 2005;129(1):156-169.
Crossref Google Scholar
65

Donninger H, Hesson L, Vos M, et al. The Ras effector RASSF2 controls the PAR-4 tumor suppressor. Mol Cell Biol. 2010;30(11):2608-2620.
Crossref Google Scholar
66

Payne SR, Serth J, Schostak M, et al. DNA methylation biomarkers of prostate cancer: confirmation of candidates and evidence urine is the most sensitive body fluid for non-invasive detection. The Prostate. 2009;69(12):1257-1269.
Crossref Google Scholar
67

Perez-Janices N, Blanco-Lugin I, Tunon MT, et al. EPB41L3, TSP-1 and RASSF2 as new clinically relevant prognostic biomarkers in diffuse gliomas. Oncotarget. 2015;6(1):368-380.
Crossref Google Scholar
68

Song H, Oh S, Oh HJ, Lim DS. Role of the tumor suppressor RASSF2 in regulation of MST1 kinase activity. Biochem Biophys Res Commun. 2010;391(1):969-973.
Crossref Google Scholar
69

Cooper WN, Hesson LB, Matallanas D, et al. RASSF2 associates with and stabilizes the proapoptotic kinase MST2. Oncogene. 2009;28(33):2988-2998.
Crossref Google Scholar
70

Imai T, Toyota M, Suzuki H, et al. Epigenetic inactivation of RASSF2 in oral squamous cell carcinoma. Cancer Sci. 2008;99(5):958-966.
Crossref Google Scholar
71

Burghel GJ, Lin WY, Whitehouse H, et al. Identification of candidate driver genes in common focal chromosomal aberrations of microsatellite stable colorectal cancer. PLoS One. 2013;8(12):e83859.
Crossref Google Scholar
72

Safavi S, Hansson M, Karlsson K, Bilogalv A, Johansson B, Paulsson K. Novel gene targets detected by genomic profiling in a consecutive series of 126 adults with acute lymphoblastic leukemia. Haematologica. 2015;100(1):55-61.
Crossref Google Scholar
73

Guo H, Liu H, Wei J, et al. Functional single nucleotide polymorphisms of the RASSF3 gene and susceptibility to squamous cell carcinoma of the head and neck. Eur J Cancer. 2014;50(3):582-592.
Crossref Google Scholar
74

Peng H, Liu H, Zhao S, Wu J, Fan J, Liao J. Silencing of RASSF3 by DNA hypermethylation is associated with tumorigenesis in somatotroph adenomas. PLoS One. 2013;8(3):e59024.
Crossref Google Scholar
75

Kudo T, Ikeda M, Nishikawa M, et al. The RASSF3 candidate tumor suppressor induces apoptosis and G1-S cell-cycle arrest via p53. Cancer Res. 2012;72(11):2901-2911.
Crossref Google Scholar
76

Eckfeld K, Hesson L, Vos MD, Bieche I, Latif F, Clark GJ. RASSF4/AD037 is a potential ras effector/tumor suppressor of the RASSF family. Cancer Res. 2004;64(23):8688-8693.
Crossref Google Scholar
77

Chow LS, Lo KW, Kwong J, Wong AY, Huang DP. Aberrant methylation of RASSF4/AD037 in nasopharyngeal carcinoma. Oncol Rep. 2004;12(4):781-787.
Crossref Google Scholar
78

Michifuri Y, Hirohashi Y, Torigoe T, et al. Small proline-rich protein-1B is overexpressed in human oral squamous cell cancer stem-like cells and is related to their growth through activation of MAP kinase signal. Biochem Biophys Res Commun. 2013;439(1):96-102.
Crossref Google Scholar
79

Crose LE, Galindo KA, Kephart JG, et al. Alveolar rhabdomyosarcoma-associated PAX3-FOXO1 promotes tumorigenesis via Hippo pathway suppression. J Clin Investig. 2014;124(1):285-296.
Crossref Google Scholar
80

Allen NP, Donninger H, Vos MD, et al. RASSF6 is a novel member of the RASSF family of tumor suppressors. Oncogene. 2007;26(42):6203-6211.
Crossref Google Scholar
81

Ikeda M, Hirabayashi S, Fujiwara N, et al. Ras-association domain family protein 6 induces apoptosis via both caspase-dependent and caspase-independent pathways. Exp Cell Res. 2007;313(7):1484-1495.
Crossref Google Scholar
82

Keramatinia A, Ahadi A, Akbari ME, et al. Genomic profiling of chronic myelogenous leukemia: basic and clinical approach. J Cancer Prev. 2017;22(2):74-81.
Crossref Google Scholar
83

Taghavi A, Akbari ME, Hashemi-Bahremani M, et al. Gene expression profiling of the 8q22-24 position in human breast cancer: TSPYL5, MTDH, ATAD2 and CCNE2 genes are implicated in oncogenesis, while WISP1 and EXT1 genes may predict a risk of metastasis. Oncol Lett. 2016;12(5):3845-3855.
Crossref Google Scholar
84

Nooshinfar E, Bashash D, Abbasalizadeh M, Safaroghli-Azar A, Sadreazami P, Akbari ME. The molecular mechanisms of tobacco in cancer pathogenesis. Iran J Cancer Prev. 2017;10(1):e7902.
Crossref Google Scholar
Genes & Diseases
Volume 6 Issue 4,
December 2019
Pages 378-384
DOI: 10.1016/j.gendis.2019.07.008
Cite this article:
Zinatizadeh MR, Momeni SA, Zarandi PK, et al. The Role and Function of Ras-association domain family in Cancer: A Review. Genes & Diseases, 2019, 6(4): 378-384. https://doi.org/10.1016/j.gendis.2019.07.008

323

Views

3

Downloads

49

Crossref

N/A

Web of Science

48

Scopus

0

CSCD

Altmetrics
Received: 14 April 2019
Revised: 16 July 2019
Accepted: 18 July 2019
Published: 27 July 2019
© 2019, Chongqing Medical University.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Return