RNF20 and histone H2B ubiquitylation exert opposing effects in basal-like versus luminal breast cancer.
Authors
Tarcic, OhadGranit, Roy Z
Pateras, Ioannis S
Masury, Hadas
Maly, Bella
Zwang, Yaara
Yarden, Yosef
Gorgoulis, Vassilis G
Pikarsky, Eli
Ben-Porath, Ittai
Oren, Moshe
Affiliation
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, IsraelIssue Date
2017-02-03
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Breast cancer subtypes display distinct biological traits that influence their clinical behavior and response to therapy. Recent studies have highlighted the importance of chromatin structure regulators in tumorigenesis. The RNF20-RNF40 E3 ubiquitin ligase complex monoubiquitylates histone H2B to generate H2Bub1, while the deubiquitinase (DUB) USP44 can remove this modification. We found that RNF20 and RNF40 expression and global H2Bub1 are relatively low, and USP44 expression is relatively high, in basal-like breast tumors compared with luminal tumors. Consistent with a tumor-suppressive role, silencing of RNF20 in basal-like breast cancer cells increased their proliferation and migration, and their tumorigenicity and metastatic capacity, partly through upregulation of inflammatory cytokines. In contrast, in luminal breast cancer cells, RNF20 silencing reduced proliferation, migration and tumorigenic and metastatic capacity, and compromised estrogen receptor transcriptional activity, indicating a tumor-promoting role. Notably, the effects of USP44 silencing on proliferation and migration in both cancer subtypes were opposite to those of RNF20 silencing. Hence, RNF20 and H2Bub1 have contrasting roles in distinct breast cancer subtypes, through differential regulation of key transcriptional programs underpinning the distinctive traits of each subtype.Cell Death and Differentiation advance online publication, 3 February 2017; doi:10.1038/cdd.2016.126.Citation
RNF20 and histone H2B ubiquitylation exert opposing effects in basal-like versus luminal breast cancer. 2017, Cell Death Differ.Journal
Cell Death and DifferentiationDOI
10.1038/cdd.2016.126PubMed ID
28157208Type
ArticleLanguage
enISSN
1476-5403ae974a485f413a2113503eed53cd6c53
10.1038/cdd.2016.126
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