Modulation of EZH2 expression by MEK-ERK or PI3K-AKT signaling in lung cancer is dictated by different KRAS oncogene mutations

Cancer Research

Volumn 76, Issue 3, 2016, Pages 675-685

  Riquelme, Erick ^a   Behrens, Carmen ^a   Lin, Heather Y ^a   Simon, George ^a   Papadimitrakopoulou, Vassiliki ^a   Izzo, Julie ^a   Moran, Cesar ^a   Kalhor, Neda ^a   Jack Lee, J ^a   Minna, John D ^b   Wistuba, Ignacio I ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; STAT3 PROTEIN; TRANSCRIPTION FACTOR EZH2; EZH2 PROTEIN, HUMAN; POLYCOMB REPRESSIVE COMPLEX 2; RAS PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; FEMALE; GENE MUTATION; HISTONE METHYLATION; HUMAN; HUMAN CELL; HUMAN TISSUE; LUNG CANCER; MAJOR CLINICAL STUDY; MOUSE; NONHUMAN; ONCOGENE K RAS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; ADENOCARCINOMA; ANIMAL; BIOSYNTHESIS; GENETIC TRANSFECTION; GENETICS; LUNG TUMOR; METABOLISM; MUTATION; NUDE MOUSE; ONCOGENE RAS; PHOSPHORYLATION; TUMOR CELL LINE; XENOGRAFT;

ADENOCARCINOMA; ANIMALS; CELL LINE, TUMOR; ENHANCER OF ZESTE HOMOLOG 2 PROTEIN; FEMALE; GENES, RAS; HETEROGRAFTS; HUMANS; LUNG NEOPLASMS; MAP KINASE SIGNALING SYSTEM; MICE; MICE, NUDE; MUTATION; PHOSPHATIDYLINOSITOL 3-KINASES; PHOSPHORYLATION; POLYCOMB REPRESSIVE COMPLEX 2; RAS PROTEINS; TRANSFECTION;

EID: 84958231381     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-15-1141     Document Type: Article

References (47)

1. Yu J, CaoQ,Mehra R, Laxman B,Tomlins SA, CreightonCJ, et al. Integrative genomics analysis reveals silencing of beta-Adrenergic signaling by polycomb in prostate cancer. Cancer Cell 2007;12:419-31.
2. Cao Q, Yu J, Dhanasekaran SM, Kim JH, Mani RS, Tomlins SA, et al. Repression of E-cadherin by the polycomb group protein EZH2 in cancer. Oncogene 2008;27:7274-84.
3. Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG, et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 2002;419:624-9.
4. Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P, et al. Role of histone H3 lysine 27methylation in Polycomb-group silencing. Science 2002;298:1039-43.
5. Fujii S, Ochiai A. Enhancer of zeste homolog 2 downregulates E-cadherin by mediating histone H3 methylation in gastric cancer cells. Cancer Sci 2008;99:738-46.
6. Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA, et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci U S A 2003;100:11606-11.
7. Huqun, Ishikawa R, Zhang J, Miyazawa H, Goto Y, Shimizu Y, et al. Enhancer of zeste homolog 2 is a novel prognostic biomarker in nonsmall cell lung cancer. Cancer 2012;118:1599-606.
8. Behrens C, Solis LM, Lin H, Yuan P, Tang X, Kadara H, et al. EZH2 protein expression associates with the early pathogenesis, tumor progression, and prognosis of non-small cell lung carcinoma. Clin Cancer Res 2013;19: 6556-65.
9. Riquelme E, Suraokar M, Behrens C, Lin HY, Girard L, Nilsson MB, et al. VEGF/VEGFR-2 upregulates EZH2 expression in lung adenocarcinoma cells and EZH2 depletion enhances the response to platinum-based and VEGFR-2-Targeted therapy. Clin Cancer Res 2014;20:3849-61.
10. Malumbres M, Barbacid M. RAS oncogenes: The first 30 years. Nat Rev Cancer 2003;3:459-65.
11. Kranenburg O. The KRAS oncogene: past, present, and future. Biochim Biophys Acta 2005;1756:81-2.
12. Kanda M, Matthaei H, Wu J, Hong SM, Yu J, Borges M, et al. Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia. Gastroenterology 2012;142:730-3.
13. Andreyev HJ, Norman AR, CunninghamD,Oates JR, Clarke PA. Kirsten ras mutations in patients with colorectal cancer: The multicenter "RASCAL" study. J Natl Cancer Inst 1998;90:675-84.
14. Siegfried JM, Gillespie AT, Mera R, Casey TJ, Keohavong P, Testa JR, et al. Prognostic value of specific KRAS mutations in lung adenocarcinomas. Cancer Epidemiol Biomarkers Prev 1997;6:841-7.
15. RaponiM, Winkler H, Dracopoli NC. KRAS mutations predict response to EGFR inhibitors. Curr Opin Pharmacol 2008;8:413-8.
16. Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 2003;3:11-22.
17. Miller MS, Miller LD. RAS mutations and oncogenesis: not all RAS mutations are created equally. Front Genet 2011;2:100.
18. Hunt JD, Strimas A, Martin JE, Eyer M, Haddican M, Luckett BG, et al. Differences in KRAS mutation spectrum in lung cancer cases between African Americans and Caucasians after occupational or environmental exposure to known carcinogens. Cancer Epidemiol Biomarkers Prev 2002;11:1405-12.
19. Berndt N, Hamilton AD, Sebti SM. Targeting protein prenylation for cancer therapy. Nat Rev Cancer 2011;11:775-91.
20. Cespedes MV, Sancho FJ, Guerrero S, Parreno M, Casanova I, Pavon MA, et al. K-ras Asp12 mutant neither interacts with Raf, nor signals through Erk and is less tumorigenic than K-ras Val12. Carcinogenesis 2006; 27:2190-200.
21. Garassino MC, Marabese M, Rusconi P, Rulli E, Martelli O, Farina G, et al. Different types of K-Ras mutations could affect drug sensitivity and tumour behaviour in non-small-cell lung cancer. Ann Oncol 2011;22: 235-7.
22. Ihle NT, Byers LA, Kim ES, Saintigny P, Lee JJ, Blumenschein GR, et al. Effect of KRAS oncogene substitutions on protein behavior: implications for signaling and clinical outcome. J Natl Cancer Inst 2012;104: 228-39.
23. Cully M, You H, Levine AJ, Mak TW. Beyond PTEN mutations: The PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer 2006;6:184-92.
24. Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science 2004;304:554.
25. Castellano E, Downward J. RAS interaction with PI3K: more than just another effector pathway. Genes Cancer 2011;2:261-74.
26. Cha TL, Zhou BP, Xia W, Wu Y, Yang CC, Chen CT, et al. Akt-mediated phosphorylation of EZH2 suppresses methylation of lysine 27 in histone H3. Science 2005;310:306-10.
27. Huang J, Perez-Burgos L, Placek BJ, Sengupta R, Richter M, Dorsey JA, et al. Repression of p53 activity by Smyd2-mediated methylation. Nature 2006;444:629-32.
28. Stark GR, Wang Y, Lu T. Lysine methylation of promoter-bound transcription factors and relevance to cancer. Cell Res 2011;21:375-80.
29. Kim E, Kim M, Woo DH, Shin Y, Shin J, Chang N, et al. Phosphorylation of EZH2 activates STAT3 signaling via STAT3 methylation and promotes tumorigenicity of glioblastoma stem-like cells. Cancer Cell 2013;23: 839-52.
30. 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.
31. Sato M, Vaughan MB, Girard L, Peyton M, Lee W, Shames DS, et al. Multiple oncogenic changes (K-RAS(V12), p53 knockdown, mutant EGFRs, p16 bypass, telomerase) are not sufficient to confer a full malignant phenotype on human bronchial epithelial cells. Cancer Res 2006;66:2116-28.
32. Ramirez RD, Sheridan S, Girard L, Sato M, Kim Y, Pollack J, et al. Immortalization of human bronchial epithelial cells in the absence of viral oncoproteins. Cancer Res 2004;64:9027-34.
33. Yang J, Huang J, Dasgupta M, Sears N, Miyagi M, Wang B, et al. Reversible methylation of promoter-bound STAT3 by histone-modifying enzymes. Proc Natl Acad Sci U S A 2010;107:21499-504.
34. Sunaga N, Shames DS, Girard L, Peyton M, Larsen JE, Imai H, et al. Knockdown of oncogenic KRAS in non-small cell lung cancers suppresses tumor growth and sensitizes tumor cells to targeted therapy. Mol Cancer Ther 2011;10:336-46.
35. Rizzo S, Hersey JM,Mellor P, Dai W, Santos-Silva A, Liber D, et al. Ovarian cancer stem cell-like side populations are enriched following chemotherapy and overexpress EZH2. Mol Cancer Ther 2011;10:325-35.
36. Paul TA, Bies J, Small D, Wolff L. Signatures of polycomb repression and reduced H3K4 trimethylation are associated with p15INK4b DNA methylation in AML. Blood 2010;115:3098-108.
37. Kotake Y, Cao R, Viatour P, Sage J, Zhang Y, Xiong Y. pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4alpha tumor suppressor gene. Genes Dev 2007;21:49-54.
38. Bracken AP, Kleine-Kohlbrecher D, Dietrich N, Pasini D, Gargiulo G, Beekman C, et al. The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev 2007;21:525-30.
39. Yang X, Karuturi RK, Sun F, Aau M, Yu K, Shao R, et al. CDKN1C (p57) is a direct target of EZH2 and suppressed by multiple epigenetic mechanisms in breast cancer cells. PLoS One 2009;4:e5011.
40. Zhang R, Wang R, Chang H, Wu F, Liu C, Deng D, et al. Downregulation of Ezh2 expression by RNA interference induces cell cycle arrest in the G0/G1 phase and apoptosis in U87 human glioma cells. Oncol Rep 2012;28: 2278-84.
41. Wu ZL, Zheng SS, Li ZM, Qiao YY, Aau MY, Yu Q. Polycomb protein EZH2 regulates E2F1-dependent apoptosis through epigenetically modulating Bim expression. Cell Death Differ 2010;17:801-10.
42. Gazin C, Wajapeyee N, Gobeil S, Virbasius CM, Green MR. An elaborate pathway required for Ras-mediated epigenetic silencing. Nature 2007; 449:1073-7.
43. Juergens RA, Wrangle J, Vendetti FP,Murphy SC, Zhao M, Coleman B, et al. Combination epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancer. Cancer Discov 2011;1:598-607.
44. Wrangle J, Wang W, Koch A, Easwaran H, Mohammad HP, Vendetti F, et al. Alterations of immune response of non-small cell lung cancer with azacytidine. Oncotarget 2013;4:2067-79.
45. Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: A leading role for STAT3. Nat Rev Cancer 2009;9:798-809.
46. Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, et al. Stat3 as an oncogene. Cell 1999;98:295-303.
47. Yue P, Turkson J. Targeting STAT3 in cancer: how successful are we? Expert Opin Investig Drugs 2009;18:45-56.