The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to drive synovial sarcoma Journal Article

Authors: Banito, A.; Li, X.; Laporte, A. N.; Roe, J. S.; Sanchez-Vega, F.; Huang, C. H.; Dancsok, A. R.; Hatzi, K.; Chen, C. C.; Tschaharganeh, D. F.; Chandwani, R.; Tasdemir, N.; Jones, K. B.; Capecchi, M. R.; Vakoc, C. R.; Schultz, N.; Ladanyi, M.; Nielsen, T. O.; Lowe, S. W.
Article Title: The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to drive synovial sarcoma
Abstract: Synovial sarcoma is an aggressive cancer invariably associated with a chromosomal translocation involving genes encoding the SWI-SNF complex component SS18 and an SSX (SSX1 or SSX2) transcriptional repressor. Using functional genomics, we identify KDM2B, a histone demethylase and component of a non-canonical polycomb repressive complex 1 (PRC1.1), as selectively required for sustaining synovial sarcoma cell transformation. SS18-SSX1 physically interacts with PRC1.1 and co-associates with SWI/SNF and KDM2B complexes on unmethylated CpG islands. Via KDM2B, SS18-SSX1 binds and aberrantly activates expression of developmentally regulated genes otherwise targets of polycomb-mediated repression, which is restored upon KDM2B depletion, leading to irreversible mesenchymal differentiation. Thus, SS18-SSX1 deregulates developmental programs to drive transformation by hijacking a transcriptional repressive complex to aberrantly activate gene expression. Banito et al. show that SS18-SSX fusions characteristic of synovial sarcoma associate with KDM2B-PRC1.1, a non-canonical polycomb repressive complex 1, to aberrantly activate the expression of developmentally regulated transcription factors that are normally targets of polycomb-mediated gene repression. © 2018 Elsevier Inc.
Keywords: controlled study; human tissue; unclassified drug; oncoprotein; human cell; nonhuman; protein domain; cell proliferation; animal cell; mouse; animal tissue; gene expression; protein depletion; protein protein interaction; animal experiment; animal model; in vivo study; dna methylation; carcinogenesis; sarcoma; gene activation; epigenetics; cell transformation; cpg island; gene fusion; synovial sarcoma; bmi1 protein; short hairpin rna; functional genomics; histone demethylase; enzyme repression; swi/snf; human; female; priority journal; article; crispr-cas9 system; crispr/cas9-mediated endogenous protein tagging; non-canonical polycomb repressive complex; oncogenic gene fusion; kdm2b enzyme; ss18 ssx1 oncoprotein; ss18 ssx2 oncoprotein; synovial sarcoma cell
Journal Title: Cancer Cell
Volume: 33
Issue: 3
ISSN: 1535-6108
Publisher: Cell Press  
Date Published: 2018-03-12
Start Page: 527
End Page: 541.e8
Language: English
DOI: 10.1016/j.ccell.2018.01.018
PROVIDER: scopus
PMCID: PMC5881394
PUBMED: 29502955
Notes: Article -- Export Date: 2 April 2018 -- Source: Scopus
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