RhoE is required for contact inhibition and negatively regulates tumor initiation and progression

Oncotarget

Volumn 6, Issue 19, 2015, Pages 17479-17490

  Hernández Sánchez, Marta ^a,d   Poch, Enric ^a   Guasch, Rosa M ^b   Ortega, Joaquín ^a   López Almela, Inmaculada ^a   Palmero, Ignacio ^c   Pérez Roger, Ignacio ^a  

^a UNIVERSIDAD CEU CARDENAL HERRERA   (Spain)

^b CENTRO DE INVESTIGACIÓN PRÍNCIPE FELIPE   (Spain)

^c INSTITUTO DE INVESTIGACIONES BIOMÉDICAS ALBERTO SOLS   (Spain)

^d UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

Author keywords

Contact inhibition; Metastasis; p27Kip1; RhoE; Tumor suppression

Indexed keywords

CYCLIN DEPENDENT KINASE INHIBITOR 1B; GUANOSINE TRIPHOSPHATASE; RHOE PROTEIN; UNCLASSIFIED DRUG; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; RND3 PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER CELL; CANCER GROWTH; CANCER INHIBITION; CANCER SUSCEPTIBILITY; CELL IMMORTALIZATION; CELL PROLIFERATION; CONTACT INHIBITION; CONTROLLED STUDY; EMBRYO; ENZYME ACTIVITY; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MALIGNANT TRANSFORMATION; MOUSE; NONHUMAN; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN TRANSPORT; SKIN TUMOR; TUMOR PROMOTION; ANIMAL; CELL TRANSFORMATION; DISEASE COURSE; EXPERIMENTAL NEOPLASM; IMMUNOHISTOCHEMISTRY; KNOCKOUT MOUSE; METABOLISM; NUDE MOUSE; PATHOLOGY; PHYSIOLOGY; WESTERN BLOTTING;

ANIMALS; BLOTTING, WESTERN; CELL TRANSFORMATION, NEOPLASTIC; CONTACT INHIBITION; DISEASE PROGRESSION; IMMUNOHISTOCHEMISTRY; MICE; MICE, KNOCKOUT; MICE, NUDE; NEOPLASMS, EXPERIMENTAL; RHO GTP-BINDING PROTEINS;

EID: 84938233255     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.4127     Document Type: Article

References (52)

1. Guasch RM, Scambler P, Jones GE and Ridley AJ. RhoE regulates actin cytoskeleton organization and cell migration. Mol Cell Biol. 1998; 18:4761-4771.
2. Komander D, Garg R, Wan PT, Ridley AJ and Barford D. Mechanism of multi-site phosphorylation from a ROCK-I:RhoE complex structure. The EMBO journal. 2008; 27:3175-3185.
3. Riento K, Guasch RM, Garg R, Jin B and Ridley AJ. RhoE binds to ROCK I and inhibits downstream signaling. Mol Cell Biol. 2003; 23:4219-4229.
4. Foster R, Hu KQ, Lu Y, Nolan KM, Thissen J and Settleman J. Identification of a novel human Rho protein with unusual properties: GTPase deficiency and in vivo farnesylation. Mol Cell Biol. 1996; 16:2689-2699.
5. Chardin P. Function and regulation of Rnd proteins. Nat Rev Mol Cell Biol. 2006; 7:54-62.
6. Villalonga P, Guasch RM, Riento K and Ridley AJ. RhoE inhibits cell cycle progression and Ras-induced transformation. Mol Cell Biol. 2004; 24:7829-7840.
7. Bektic J, Pfeil K, Berger AP, Ramoner R, Pelzer A, Schafer G, Kofler K, Bartsch G and Klocker H. Small G-protein RhoE is underexpressed in prostate cancer and induces cell cycle arrest and apoptosis. The Prostate. 2005; 64:332-340.
8. Poch E, Minambres R, Mocholi E, Ivorra C, Perez-Arago A, Guerri C, Perez-Roger I and Guasch RM. RhoE interferes with Rb inactivation and regulates the proliferation and survival of the U87 human glioblastoma cell line. Exp Cell Res. 2007; 313:719-731.
9. Lonjedo M, Poch E, Mocholi E, Hernandez-Sanchez M, Ivorra C, Franke TF, Guasch RM and Perez-Roger I. The Rho family member RhoE interacts with Skp2 and is degraded at the proteasome during cell cycle progression. The Journal of biological chemistry. 2013; 288:30872-30882.
10. Boswell SA, Ongusaha PP, Nghiem P and Lee SW. The protective role of a small GTPase RhoE against UVB-induced DNA damage in keratinocytes. The Journal of biological chemistry. 2007; 282:4850-4858.
11. Ongusaha PP, Kim HG, Boswell SA, Ridley AJ, Der CJ, Dotto GP, Kim YB, Aaronson SA and Lee SW. RhoE is a pro-survival p53 target gene that inhibits ROCK I-mediated apoptosis in response to genotoxic stress. Current biology : CB. 2006; 16:2466-2472.
12. Belgiovine C, Frapolli R, Bonezzi K, Chiodi I, Favero F, Mello-Grand M, Dei Tos AP, Giulotto E, Taraboletti G, D'Incalci M and Mondello C. Reduced expression of the ROCK inhibitor Rnd3 is associated with increased invasiveness and metastatic potential in mesenchymal tumor cells. PloS one. 2010; 5:e14154.
13. Grise F, Sena S, Bidaud-Meynard A, Baud J, Hiriart JB, Makki K, Dugot-Senant N, Staedel C, Bioulac-Sage P, Zucman-Rossi J, Rosenbaum J and Moreau V. Rnd3/RhoE Is down-regulated in hepatocellular carcinoma and controls cellular invasion. Hepatology. 2012; 55:1766-1775.
14. Luo H, Dong Z, Zou J, Zeng Q, Wu D and Liu L. Down-regulation of RhoE is associated with progression and poor prognosis in hepatocellular carcinoma. J Surg Oncol. 2012; 105:699-704.
15. Zhu Z, Todorova K, Lee KK, Wang J, Kwon E, Kehayov I, Kim HG, Kolev V, Dotto GP, Lee SW and Mandinova A. Small GTPase RhoE/Rnd3 Is a Critical Regulator of Notch1 Signaling. Cancer Res. 2014; 74:2082-2093.
16. Chen J, Zhou H, Li Q, Qiu M, Li Z, Tang Q, Liu M, Zhu Y, Huang J, Lang N, Liu Z, Deng Y, Zhang S and Bi F. Epigenetic modification of RhoE expression in gastric cancer cells. Oncol Rep. 2011; 25:173-180.
17. Fu Y, Liu X, Zhou N, Du L, Sun Y, Zhang X and Ge Y. MicroRNA-200b stimulates tumour growth in TGFBR2-null colorectal cancers by negatively regulating p27/kip1. J Cell Physiol. 2014; 229:772-782.
18. Hidalgo-Carcedo C, Hooper S, Chaudhry SI, Williamson P, Harrington K, Leitinger B and Sahai E. Collective cell migration requires suppression of actomyosin at cell-cell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6. Nature cell biology. 2011; 13:49-58.
19. Pinner S and Sahai E. PDK1 regulates cancer cell motility by antagonising inhibition of ROCK1 by RhoE. Nature cell biology. 2008; 10:127-137.
20. Cuiyan Z, Jie H, Fang Z, Kezhi Z, Junting W, Susheng S, Xiaoli F, Ning L, Xinhua M, Zhaoli C, Kang S, Bin Q, Baozhong L, Sheng C and Meihua X. Overexpression of RhoE in Non-small Cell Lung Cancer (NSCLC) is associated with smoking and correlates with DNA copy number changes. Cancer biology & therapy. 2007; 6:335-342.
21. Zhang C, Zhou F, Li N, Shi S, Feng X, Chen Z, Hang J, Qiu B, Li B, Chang S, Wan J, Shao K, Xing X, Tan X, Wang Z, Xiong M, et al. Overexpression of RhoE has a prognostic value in non-small cell lung cancer. Ann Surg Oncol. 2007; 14:2628-2635.
22. Feng B, Li K, Zhong H, Ren G, Wang H, Shang Y, Bai M, Liang J, Wang X and Fan D. RhoE promotes metastasis in gastric cancer through a mechanism dependent on enhanced expression of CXCR4. PloS one. 2013; 8:e81709.
23. Trojan L, Schaaf A, Steidler A, Haak M, Thalmann G, Knoll T, Gretz N, Alken P and Michel MS. Identification of metastasis-associated genes in prostate cancer by genetic profiling of human prostate cancer cell lines. Anticancer research. 2005; 25:183-191.
24. Zhou J, Li K, Gu Y, Feng B, Ren G, Zhang L, Wang Y, Nie Y and Fan D. Transcriptional up-regulation of RhoE by hypoxia-inducible factor (HIF)-1 promotes epithelial to mesenchymal transition of gastric cancer cells during hypoxia. Biochemical and biophysical research communications. 2011; 415:348-354.
25. Zhou J, Yang J, Li K, Mo P, Feng B, Wang X, Nie Y and Fan D. RhoE is associated with relapse and prognosis of patients with colorectal cancer. Ann Surg Oncol. 2013; 20:175-182.
26. Klein RM and Aplin AE. Rnd3 regulation of the actin cytoskeleton promotes melanoma migration and invasive outgrowth in three dimensions. Cancer Res. 2009; 69:2224-2233.
27. Mocholi E, Ballester-Lurbe B, Arque G, Poch E, Peris B, Guerri C, Dierssen M, Guasch RM, Terrado J and Perez-Roger I. RhoE deficiency produces postnatal lethality, profound motor deficits and neurodevelopmental delay in mice. PloS one. 2011; 6:e19236.
28. St Croix B, Sheehan C, Rak JW, Florenes VA, Slingerland JM and Kerbel RS. E-Cadherin-dependent growth suppression is mediated by the cyclin-dependent kinase inhibitor p27(KIP1). The Journal of cell biology. 1998; 142:557-571.
29. Levenberg S, Yarden A, Kam Z and Geiger B. p27 is involved in N-cadherin-mediated contact inhibition of cell growth and S-phase entry. Oncogene. 1999; 18:869-876.
30. Motti ML, Califano D, Baldassarre G, Celetti A, Merolla F, Forzati F, Napolitano M, Tavernise B, Fusco A and Viglietto G. Reduced E-cadherin expression contributes to the loss of p27kip1-mediated mechanism of contact inhibition in thyroid anaplastic carcinomas. Carcinogenesis. 2005; 26:1021-1034.
31. Blagosklonny MV. Are p27 and p21 cytoplasmic oncoproteins? Cell cycle. 2002; 1:391-393.
32. Serres MP, Zlotek-Zlotkiewicz E, Concha C, Gurian-West M, Daburon V, Roberts JM and Besson A. Cytoplasmic p27 is oncogenic and cooperates with Ras both in vivo and in vitro. Oncogene. 2011; 30:2846-2858.
33. Todaro GJ and Green H. Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. The Journal of cell biology. 1963; 17:299-313.
34. Kemp CJ. Multistep skin cancer in mice as a model to study the evolution of cancer cells. Seminars in cancer biology. 2005; 15:460-473.
35. Quintanilla M, Brown K, Ramsden M and Balmain A. Carcinogen-specific mutation and amplification of Ha-ras during mouse skin carcinogenesis. Nature. 1986; 322:78-80.
36. Minn AJ, Gupta GP, Siegel PM, Bos PD, Shu W, Giri DD, Viale A, Olshen AB, Gerald WL and Massague J. Genes that mediate breast cancer metastasis to lung. Nature. 2005; 436:518-524.
37. Nguyen DX, Bos PD and Massague J. Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer. 2009; 9:274-284.
38. Chu IM, Hengst L and Slingerland JM. The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy. Nat Rev Cancer. 2008; 8:253-267.
39. Hanahan D and Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144:646-674.
40. Leontieva OV, Demidenko ZN and Blagosklonny MV. Contact inhibition and high cell density deactivate the mammalian target of rapamycin pathway, thus suppressing the senescence program. Proceedings of the National Academy of Sciences of the United States of America. 2014; 111:8832-8837.
41. Lu Z and Hunter T. Ubiquitylation and proteasomal degradation of the p21(Cip1), p27(Kip1) and p57(Kip2) CDK inhibitors. Cell cycle. 2010; 9:2342-2352.
42. Andreu EJ, Lledo E, Poch E, Ivorra C, Albero MP, Martinez-Climent JA, Montiel-Duarte C, Rifon J, Perez-Calvo J, Arbona C, Prosper F and Perez-Roger I. BCR-ABL induces the expression of Skp2 through the PI3K pathway to promote p27Kip1 degradation and proliferation of chronic myelogenous leukemia cells. Cancer Res. 2005; 65:3264-3272.
43. Borriello A, Cucciolla V, Oliva A, Zappia V and Della Ragione F. p27Kip1 metabolism: a fascinating labyrinth. Cell cycle. 2007; 6:1053-1061.
44. Liebig T, Erasmus J, Kalaji R, Davies D, Loirand G, Ridley A and Braga VM. RhoE Is required for keratinocyte differentiation and stratification. Molecular biology of the cell. 2009; 20:452-463.
45. Madigan JP, Bodemann BO, Brady DC, Dewar BJ, Keller PJ, Leitges M, Philips MR, Ridley AJ, Der CJ and Cox AD. Regulation of Rnd3 localization and function by protein kinase C alpha-mediated phosphorylation. Biochem J. 2009; 424:153-161.
46. Riento K, Totty N, Villalonga P, Garg R, Guasch R and Ridley AJ. RhoE function is regulated by ROCK I-mediated phosphorylation. The EMBO journal. 2005; 24:1170-1180.
47. Pinner S and Sahai E. Imaging amoeboid cancer cell motility in vivo. J Microsc. 2008; 231:441-445.
48. Zambrowicz BP, Friedrich GA, Buxton EC, Lilleberg SL, Person C and Sands AT. Disruption and sequence identification of 2,000 genes in mouse embryonic stem cells. Nature. 1998; 392:608-611.
49. Perez-Roger I, Kim SH, Griffiths B, Sewing A and Land H. Cyclins D1 and D2 mediate myc-induced proliferation via sequestration of p27(Kip1) and p21(Cip1). The EMBO journal. 1999; 18:5310-5320.
50. Albero MP, Vaquer JM, Andreu EJ, Villanueva JJ, Franch L, Ivorra C, Poch E, Agirre X, Prosper F and Perez-Roger I. Bortezomib decreases Rb phosphorylation and induces caspase-dependent apoptosis in Imatinib-sensitive and -resistant Bcr-Abl1-expressing cells. Oncogene. 2010; 29:3276-3286.
51. Hayflick L. (1973). Tissue culture: methods and applications. (New York,: Academic Press).
52. Ishida N, Hara T, Kamura T, Yoshida M, Nakayama K and Nakayama KI. Phosphorylation of p27Kip1 on serine 10 is required for its binding to CRM1 and nuclear export. The Journal of biological chemistry. 2002; 277:14355-14358.