北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 基础医学院  > 北京大学衰老研究中心  > 期刊论文
学科主题: 基础医学
题名:
FOXA1 antagonizes EZH2-mediated CDKN2A repression in carcinogenesis
作者: Zhang, Yu; Tong, Tanjun
关键词: FOXA1 ; EZH2 ; CDKN2A ; Carcinogenesis
刊名: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
发表日期: 2014-10-10
DOI: 10.1016/j.bbrc.2014.09.092
卷: 453, 期:1, 页:172-178
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Biophysics
研究领域[WOS]: Biochemistry & Molecular Biology ; Biophysics
关键词[WOS]: GENE-EXPRESSION PROFILES ; PROSTATE-CANCER ; CELLULAR SENESCENCE ; ESTROGEN-RECEPTOR ; TRANSCRIPTION ; P16(INK4A) ; CELLS
英文摘要:

CDKN2A (p16(INK4a)) is a crucial tumor suppressor involved in many cancers. Our recent investigations revealed that FOXA1 as a forkhead transcription factor mediates CDKN2A activation in cellular senescence. However, the contribution of this axis in carcinogenesis remains unclear. Here, using a comprehensive collection of cancer microarray data, we found FOXA1 is down-regulated in many cancers compared to their normal counterparts and the positive correlation between FOXA1 and CDKN2A could be observed in prostate and breast cancers with lower EZH2 (epigenetic repressor for CDKN2A) expression. Experimentally, epistasis analysis in prostate and breast cancer cells indicated that higher expression of FOXA1 opposes EZH2-mediated CDKN2A repression, as further depletion of FOXA1 reverts the de-silencing of CDKN2A caused by EZH2 inhibition. Concomitantly, EZH2-depletion suppresses cancer cell cycle progression and this regulation is optimized in the presence of FOXA1 and CDKN2A. A further oncogenic transformation assay suggested that overexpression of EZH2 is insufficient to block RAS-induced CDKN2A activation and loss of FOXA1 is mandatory to potentiate EZH2-mediated CDKN2A silencing and to bypass the senescence barrier. Importantly, using an in vitro histone methyltransferase (HMTase) system, we found FOXA1 directly inhibits EZH2′s histone methyltransferase activity through its C-terminal histone binding motif. These data support that positive regulation of CDKN2A by FOXA1 counteracts its tumorigenic repression of by EZH2 in cancers. (C) 2014 Elsevier Inc. All rights reserved.

语种: 英语
所属项目编号: 81300254 ; 2013CB530801
项目资助者: National Basic Research Programs of China ; National Key Basic Research Program of China
WOS记录号: WOS:000343634900029
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58425
Appears in Collections:基础医学院_北京大学衰老研究中心_期刊论文

Files in This Item:
File Name/ File Size Content Type Version Access License
1-s2.0-S0006291X14017203-main.pdf(1288KB)期刊论文作者接受稿限制开放 联系获取全文

作者单位: Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Res Ctr Aging, Beijing 100191, Peoples R China

Recommended Citation:
Zhang, Yu,Tong, Tanjun. FOXA1 antagonizes EZH2-mediated CDKN2A repression in carcinogenesis[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2014,453(1):172-178.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Zhang, Yu]'s Articles
[Tong, Tanjun]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Zhang, Yu]‘s Articles
[Tong, Tanjun]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace