SWI/SNF-mutant cancers depend on catalytic and non-catalytic activity of EZH2

Nature Medicine

Volumn 21, Issue 12, 2015, Pages 1491-1496

  Kim, Kimberly H ^a,b,c   Kim, Woojin ^a,b,c   Howard, Thomas P ^a,b,c   Vazquez, Francisca ^d   Tsherniak, Aviad ^d   Wu, Jennifer N ^a,b,c,d   Wang, Weishan ^a,b,c   Haswell, Jeffrey R ^a,b,c   Walensky, Loren D ^a,b,c   Hahn, William C ^a,d   Orkin, Stuart H ^a,b,c,e   Roberts, Charles W M ^a,b,c,d,e,f  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b BOSTON CHILDREN S HOSPITAL   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

^d MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^e HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^f ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BRG1 PROTEIN; HISTONE METHYLTRANSFERASE; POLYCOMB REPRESSIVE COMPLEX 2; PROTEIN SWI; RAS PROTEIN; TRANSCRIPTION FACTOR EZH2; TRANSCRIPTION FACTOR SNF; ENZYME INHIBITOR; EZH2 PROTEIN, HUMAN; GSK126; INDOLE DERIVATIVE; NONHISTONE PROTEIN; PYRIDONE DERIVATIVE; SMALL INTERFERING RNA; SWI-SNF-B CHROMATIN-REMODELING COMPLEX; TRANSCRIPTION FACTOR;

ANIMAL CELL; CANCER CELL LINE; CATALYSIS; CELL MUTANT; CELL PROLIFERATION; CONTROLLED STUDY; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME STABILITY; GENE MUTATION; HUMAN; HUMAN CELL; LETTER; MOUSE; NEOPLASM; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN PHOSPHORYLATION; PROTEIN SUBUNIT; TUMOR XENOGRAFT; ACETYLATION; ANIMAL; DRUG EFFECTS; DRUG RESISTANCE; DRUG SCREENING; FEMALE; GENETICS; METABOLISM; METHYLATION; MUTATION; NUDE MOUSE; PHOSPHORYLATION; TUMOR CELL LINE;

ACETYLATION; ANIMALS; CATALYSIS; CELL LINE, TUMOR; CHROMOSOMAL PROTEINS, NON-HISTONE; DRUG RESISTANCE, NEOPLASM; ENHANCER OF ZESTE HOMOLOG 2 PROTEIN; ENZYME INHIBITORS; FEMALE; HUMANS; INDOLES; METHYLATION; MICE, NUDE; MUTATION; NEOPLASMS; PHOSPHORYLATION; POLYCOMB REPRESSIVE COMPLEX 2; PYRIDONES; RNA, SMALL INTERFERING; TRANSCRIPTION FACTORS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84949551829     PISSN: 10788956     EISSN: 1546170X     Source Type: Journal    
DOI: 10.1038/nm.3968     Document Type: Letter

References (41)

1. Kadoch, C. et al. Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy. Nat. Genet. 45, 592-601 (2013).
2. Wu, J.I., Lessard, J. & Crabtree, G.R. Understanding the words of chromatin regulation. Cell 136, 200-206 (2009).
3. Wilson, B.G. & Roberts, C.W. SWI/SNF nucleosome remodellers and cancer. Nat. Rev. Cancer 11, 481-492 (2011).
4. Weissman, B. & Knudsen, K.E. Hijacking the chromatin remodeling machinery: Impact of SWI/SNF perturbations in cancer. Cancer Res. 69, 8223-8230 (2009).
5. Guan, B. et al. Roles of deletion of Arid1a, a tumor suppressor, in mouse ovarian tumorigenesis. J. Natl. Cancer Inst. 106, dju46 (2014).
6. Bultman, S.J. et al. Characterization of mammary tumors from Brg1 heterozygous mice. Oncogene 27, 460-468 (2008).
7. Roberts, C.W., Leroux, M.M., Fleming, M.D. & Orkin, S.H. Highly penetrant, rapid tumorigenesis through conditional inversion of the tumor suppressor gene Snf5. Cancer Cell 2, 415-425 (2002).
8. Jones, S. et al. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science 330, 228-231 (2010).
9. Wiegand, K.C. et al. ARID1A mutations in endometriosis-associated ovarian carcinomas. N. Engl. J. Med. 363, 1532-1543 (2010).
10. Fujimoto, A. et al. Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators. Nat. Genet. 44, 760-764 (2012).
11. Li, M. et al. Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma. Nat. Genet. 43, 828-829 (2011).
12. Gui, Y. et al. Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder. Nat. Genet. 43, 875-878 (2011).
13. Varela, I. et al. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature 469, 539-542 (2011).
14. Parsons, D.W. et al. The genetic landscape of the childhood cancer medulloblastoma. Science 331, 435-439 (2011).
15. Robinson, G. et al. Novel mutations target distinct subgroups of medulloblastoma. Nature 488, 43-48 (2012).
16. Sausen, M. et al. Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma. Nat. Genet. 45, 12-17 (2013).
17. Shain, A.H. et al. Convergent structural alterations define SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeler as a central tumor suppressive complex in pancreatic cancer. Proc. Natl. Acad. Sci. USA 109, E252-E259 (2012).
18. Le Gallo, M. et al. Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes. Nat. Genet. 44, 1310-1315 (2012).
19. Kennison, J.A. The Polycomb and trithorax group proteins of Drosophila: Trans-regulators of homeotic gene function. Annu. Rev. Genet. 29, 289-303 (1995).
20. Shao, Z. et al. Stabilization of chromatin structure by PRC1, a Polycomb complex. Cell 98, 37-46 (1999).
21. Tamkun, J.W. et al. brahma: A regulator of Drosophila homeotic genes structurally related to the yeast transcriptional activator SNF2/SWI2. Cell 68, 561-572 (1992).
22. Ringrose, L. & Paro, R. Epigenetic regulation of cellular memory by the Polycomb and Trithorax group proteins. Annu. Rev. Genet. 38, 413-443 (2004).
23. Pasini, D., Bracken, A.P., Hansen, J.B., Capillo, M. & Helin, K. The polycomb group protein Suz12 is required for embryonic stem cell differentiation. Mol. Cell. Biol. 27, 3769-3779 (2007).
24. Cao, R. & Zhang, Y. SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex. Mol. Cell 15, 57-67 (2004).
25. Margueron, R. et al. Role of the polycomb protein EED in the propagation of repressive histone marks. Nature 461, 762-767 (2009).
26. Qi, W. et al. Selective inhibition of Ezh2 by a small-molecule inhibitor blocks tumor cells proliferation. Proc. Natl. Acad. Sci. USA 109, 21360-21365 (2012).
27. McCabe, M.T. et al. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature 492, 108-112 (2012).
28. McCabe, M.T. et al. Mutation of A677 in histone methyltransferase EZH2 in human B-cell lymphoma promotes hypertrimethylation of histone H3 on lysine 27 (H3K27). Proc. Natl. Acad. Sci. USA 109, 2989-2994 (2012).
29. Knutson, S.K. et al. A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. Nat. Chem. Biol. 8, 890-896 (2012).
30. Kia, S.K., Gorski, M.M., Giannakopoulos, S. & Verrijzer, C.P. SWI/SNF mediates polycomb eviction and epigenetic reprogramming of the INK4b-ARF-INK4a locus. Mol. Cell. Biol. 28, 3457-3464 (2008).
31. Knutson, S.K. et al. Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2. Proc. Natl. Acad. Sci. USA 110, 7922-7927 (2013).
32. Wilson, B.G. et al. Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation. Cancer Cell 18, 316-328 (2010).
33. Medina, P.P. et al. Frequent BRG1/SMARCA4-inactivating mutations in human lung cancer cell lines. Hum. Mutat. 29, 617-622 (2008).
34. Cheung, H.W. et al. Systematic investigation of genetic vulnerabilities across cancer cell lines reveals lineage-specific dependencies in ovarian cancer. Proc. Natl. Acad. Sci. USA 108, 12372-12377 (2011).
35. Shao, D.D. et al. ATARiS: Computational quantification of gene suppression phenotypes from multisample rnai screens. Genome Res. 23, 665-678 (2013).
36. Cowley, G.S. et al. Parallel genome-scale loss of function screens in 216 cancer cell lines for the identification of context-specific genetic dependencies. Sci. Data 1, 140035 (2014).
37. MacConaill, L.E. et al. Profiling critical cancer gene mutations in clinical tumor samples. PLoS ONE 4, e7887 (2009).
38. De Raedt, T. et al. PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature 514, 247-251 (2014).
39. Kim, W. et al. Targeted disruption of the EZH2-EED complex inhibits EZH2-dependent cancer. Nat. Chem. Biol. 9, 643-650 (2013).
40. Wei, Y. et al. CDK1-dependent phosphorylation of EZH2 suppresses methylation of H3K27 and promotes osteogenic differentiation of human mesenchymal stem cells. Nat. Cell Biol. 13, 87-94 (2011).
41. Xu, K. et al. EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent. Science. 338, 1465-1469 (2012).