Context-specific regulation of NF-κB target gene expression by EZH2 in breast cancers.

Abstract:

:Both EZH2 and NF-κB contribute to aggressive breast cancer, yet whether the two oncogenic factors have functional crosstalk in breast cancer is unknown. Here, we uncover an unexpected role of EZH2 in conferring the constitutive activation of NF-κB target gene expression in ER-negative basal-like breast cancer cells. This function of EZH2 is independent of its histone methyltransferase activity but requires the physical interaction with RelA/RelB to promote the expression of NF-κB targets. Intriguingly, EZH2 acts oppositely in ER-positive luminal-like breast cancer cells and represses NF-κB target gene expression by interacting with ER and directing repressive histone methylation on their promoters. Thus, EZH2 functions as a double-facet molecule in breast cancers, either as a transcriptional activator or repressor of NF-κB targets, depending on the cellular context. These findings reveal an additional mechanism by which EZH2 promotes breast cancer progression and underscore the need for developing context-specific strategy for therapeutic targeting of EZH2 in breast cancers.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Lee ST,Li Z,Wu Z,Aau M,Guan P,Karuturi RK,Liou YC,Yu Q

doi

10.1016/j.molcel.2011.08.011

subject

Has Abstract

pub_date

2011-09-02 00:00:00

pages

798-810

issue

5

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(11)00628-9

journal_volume

43

pub_type

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