The H3K9 Methyltransferase G9a Represses E-cadherin and is Associated with Myometrial Invasion in Endometrial Cancer

Annals of Surgical Oncology

Volumn 22, Issue , 2015, Pages 1556-1565

  Hsiao, Sheng Mou ^a   Chen, Min Wei ^b   Chen, Chi An ^b   Chien, Ming Hsien ^c,d   Hua, Kuo Tai ^e   Hsiao, Michael ^f   Kuo, Min Liang ^g   Wei, Lin Hung ^b  

^a FAR EASTERN MEMORIAL HOSPITAL   (Taiwan)

^b NATIONAL TAIWAN UNIVERSITY HOSPITAL   (Taiwan)

^c TAIPEI MEDICAL UNIVERSITY   (Taiwan)

^d TAIPEI MEDICAL UNIVERSITY   (Taiwan)

^e NATIONAL TAIWAN UNIVERSITY   (Taiwan)

^f GENOMICS RESEARCH CENTER   (Taiwan)

^g NATIONAL TAIWAN UNIVERSITY   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

DNA METHYLTRANSFERASE; HISTONE H3; HISTONE METHYLTRANSFERASE; HISTONE METHYLTRANSFERASE G9A; TETRACYCLINE; UNCLASSIFIED DRUG; UVOMORULIN; CADHERIN; EHMT2 PROTEIN, HUMAN; HISTOCOMPATIBILITY ANTIGEN; HISTONE LYSINE METHYLTRANSFERASE; TUMOR MARKER;

ADULT; ARTICLE; CANCER SURGERY; CANCER TISSUE; CELL MIGRATION; CONTROLLED STUDY; CORRELATION ANALYSIS; ENDOMETRIAL CANCER CELL LINE; ENDOMETRIUM CANCER; EPIGENETICS; FEMALE; GENE REPRESSION; GENE SILENCING; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; IN VITRO STUDY; IN VIVO STUDY; MAJOR CLINICAL STUDY; MYOMETRIAL INVASION; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; RNA INTERFERENCE; TUMOR INVASION; ANIMAL; ANTAGONISTS AND INHIBITORS; APOPTOSIS; CANCER GRADING; CANCER STAGING; CELL MOTION; CELL PROLIFERATION; CHROMATIN IMMUNOPRECIPITATION; ENDOMETRIUM TUMOR; ENZYME IMMUNOASSAY; GENE EXPRESSION REGULATION; GENETIC EPIGENESIS; GENETICS; METABOLISM; MIDDLE AGED; MOUSE; MYOMETRIUM; NONOBESE DIABETIC MOUSE; PATHOLOGY; PROGNOSIS; PROMOTER REGION; REAL TIME POLYMERASE CHAIN REACTION; RETROSPECTIVE STUDY; SCID MOUSE; SURVIVAL RATE; TUMOR CELL CULTURE; WESTERN BLOTTING;

ANIMALS; APOPTOSIS; BIOMARKERS, TUMOR; BLOTTING, WESTERN; CADHERINS; CELL MOVEMENT; CELL PROLIFERATION; CHROMATIN IMMUNOPRECIPITATION; ENDOMETRIAL NEOPLASMS; EPIGENESIS, GENETIC; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HISTOCOMPATIBILITY ANTIGENS; HISTONE-LYSINE N-METHYLTRANSFERASE; HUMANS; IMMUNOENZYME TECHNIQUES; MICE; MICE, INBRED NOD; MICE, SCID; MIDDLE AGED; MYOMETRIUM; NEOPLASM GRADING; NEOPLASM INVASIVENESS; NEOPLASM STAGING; PROGNOSIS; PROMOTER REGIONS, GENETIC; REAL-TIME POLYMERASE CHAIN REACTION; RETROSPECTIVE STUDIES; SURVIVAL RATE; TUMOR CELLS, CULTURED;

EID: 84952875140     PISSN: 10689265     EISSN: 15344681     Source Type: Journal    
DOI: 10.1245/s10434-015-4379-5     Document Type: Article

References (39)

1. Lachner M, O’Sullivan RJ, Jenuwein T. An epigenetic road map for histone lysine methylation. J Cell Sci. 2003;116:2117–24.
2. Tachibana M, Sugimoto K, Fukushima T, Shinkai Y. Set domain-containing protein, G9a, is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3. J Biol Chem. 2001;276:25309–17.
3. Tachibana M, Matsumura Y, Fukuda M, Kimura H, Shinkai Y. G9a/GLP complexes independently mediate H3K9 and DNA methylation to silence transcription. Embo J. 2008;27:2681–90.
4. Shinkai Y, Tachibana M. H3K9 methyltransferase G9a and the related molecule GLP. Genes Dev. 2011;25:781–8.
5. Huang J, Dorsey J, Chuikov S, et al. G9a and Glp methylate lysine 373 in the tumor suppressor p53. J Biol Chem. 2010;285:9636–41.
6. Kondo Y, Shen L, Ahmed S, Boumber Y, Sekido Y, Haddad BR, Issa JP. Downregulation of histone H3 lysine 9 methyltransferase G9a induces centrosome disruption and chromosome instability in cancer cells. Plos One. 2008;3:e2037.
7. Kang Y, Massague J. Epithelial-mesenchymal transitions: twist in development and metastasis. Cell. 2004;118:277–9.
8. Gumbiner BM. Regulation of cadherin-mediated adhesion in morphogenesis. Nat Rev Mol Cell Biol. 2005;6:622–34.
9. Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science. 1991;251:1451–5.
10. Cavallaro U, Christofori G. Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nat Rev Cancer. 2004;4:118–32.
11. Conacci-Sorrell M, Zhurinsky J, Ben-Ze’ev A. The cadherin-catenin adhesion system in signaling and cancer. J Clin Invest. 2002;109:987–91.
12. Sakuragi N, Nishiya M, Ikeda K, et al. Decreased E-cadherin expression in endometrial carcinoma is associated with tumor dedifferentiation and deep myometrial invasion. Gynecol Oncol. 1994;53:183–9.
13. Holcomb K, Delatorre R, Pedemonte B, McLeod C, Anderson L, Chambers J. E-cadherin expression in endometrioid, papillary serous, and clear cell carcinoma of the endometrium. Obstet Gynecol. 2002;100:1290–5.
14. Mell LK, Meyer JJ, Tretiakova M, et al. Prognostic significance of E-cadherin protein expression in pathological stage I–III endometrial cancer. Clin Cancer Res. 2004;10:5546–53.
15. Dong C, Wu Y, Yao J, et al. G9a interacts with Snail and is critical for Snail-mediated E-cadherin repression in human breast cancer. J Clin Invest. 2012;122:1469–86.
16. Chen MW, Hua KT, Kao HJ, et al. H3K9 histone methyltransferase G9a promotes lung cancer invasion and metastasis by silencing the cell adhesion molecule Ep-CAM. Cancer Res. 2010;70:7830–40.
17. Liu YN, Lee WW, Wang CY, et al. Regulatory mechanisms controlling human E-cadherin gene expression. Oncogene. 2005;24:8277–90.
18. Yeramian A, Moreno-Bueno G, Dolcet X, et al. Endometrial carcinoma: molecular alterations involved in tumor development and progression. Oncogene. 2013;32:403–13.
19. Wozniak RJ, Klimecki WT, Lau SS, Feinstein Y, Futscher BW. 5-Aza-2’-deoxycytidine-mediated reductions in G9A histone methyltransferase and histone H3 K9 di-methylation levels are linked to tumor suppressor gene reactivation. Oncogene. 2007;26:77–90.
20. Tao MH, Freudenheim JL. DNA methylation in endometrial cancer. Epigenetics. 2010;5:491–8.
21. Wright JD, Barrena Medel NI, Sehouli J, Fujiwara K, Herzog TJ. Contemporary management of endometrial cancer. Lancet. 2012;379:1352–60.
22. Creasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer: a Gynecologic Oncology Group study. Cancer. 1987;60:2035–41.
23. Morrow CP, Bundy BN, Kurman RJ, Creasman WT, Heller P, Homesley HD, Graham JE. Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol. 1991;40:55–65.
24. Montserrat N, Mozos A, Llobet D, et al. Epithelial-to-mesenchymal transition in early-stage endometrioid endometrial carcinoma. Hum Pathol. 2012;43:632–43.
25. Yi TZ, Guo J, Zhou L, et al. Prognostic value of E-cadherin expression and CDH1 promoter methylation in patients with endometrial carcinoma. Cancer Invest. 2011;29:86–92.
26. Saito T, Nishimura M, Yamasaki H, Kudo R. Hypermethylation in promoter region of E-cadherin gene is associated with tumor dedifferention and myometrial invasion in endometrial carcinoma. Cancer. 2003;97:1002–9.
27. Risinger JI, Berchuck A, Kohler MF, Boyd J. Mutations of the E-cadherin gene in human gynecologic cancers. Nat Genet. 1994;7:98–102.
28. Blechschmidt K, Kremmer E, Hollweck R, Mylonas I, Höfler H, Kremer M, Becker KF. The E-cadherin repressor Snail plays a role in tumor progression of endometrioid adenocarcinomas. Diagn Mol Pathol. 2007;16:222–8.
29. Singh M, Spoelstra NS, Jean A, et al. ZEB1 expression in type I vs type II endometrial cancers: a marker of aggressive disease. Mod Pathol. 2008;21:912–23.
30. McCabe MT, Brandes JC, Vertino PM. Cancer DNA methylation: molecular mechanisms and clinical implications. Clin Cancer Res. 2009;15:3927–37.
31. 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.
32. Cao Q, Yu J, Dhanasekaran SM, et al. Repression of E-cadherin by the polycomb group protein EZH2 in cancer. Oncogene. 2008;27:7274–84.
33. Rai K, Jafri IF, Chidester S, James SR, Karpf AR, Cairns BR, Jones DA. Dnmt3 and G9a cooperate for tissue-specific development in zebra fish. J Biol Chem. 2010;285:4110–21.
34. Esteve PO, Chin HG, Smallwood A, et al. Direct interaction between DNMT1 and G9a coordinates DNA and histone methylation during replication. Genes Dev. 2006;20:3089–103.
35. Vire E, Brenner C, Deplus R, et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature. 2006;439:871–4.
36. Taghavi P, van Lohuizen M. Developmental biology: two paths to silence merge. Nature. 2006;439:794–5.
37. Epsztejn-Litman S, Feldman N, Abu-Remaileh M, et al. De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes. Nat Struct Mol Biol. 2008;15:1176–83.
38. Bachman KE, Park BH, Rhee I, et al. Histone modifications and silencing prior to DNA methylation of a tumor suppressor gene. Cancer Cell. 2003;3:89–95.
39. Feldman N, Gerson A, Fang J, et al. G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis. Nat Cell Biol. 2006;8:188–94.