RNF20 and histone H2B ubiquitylation exert opposing effects in Basal-Like versus luminal breast cancer

Ohad Tarcic, Roy Z. Granit, Ioannis S. Pateras, Hadas Masury, Bella Maly, Yaara Zwang, Yosef Yarden, Vassilis G. Gorgoulis, Eli Pikarsky, Ittai Ben-Porath, Moshe Oren*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)694-704
Number of pages11
JournalCell Death and Differentiation
Volume24
Issue number4
DOIs
StatePublished - 1 Apr 2017

Bibliographical note

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© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

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