| Literature DB >> 24525235 |
Jian Shi1, Yifan Wang2, Lei Zeng3, Yadi Wu4, Jiong Deng5, Qiang Zhang3, Yiwei Lin1, Junlin Li1, Tiebang Kang6, Min Tao7, Elena Rusinova3, Guangtao Zhang3, Chi Wang8, Haining Zhu9, Jun Yao10, Yi-Xin Zeng6, B Mark Evers11, Ming-Ming Zhou12, Binhua P Zhou13.
Abstract
Twist is a key transcription activator of epithelial-mesenchymal transition (EMT). It remains unclear how Twist induces gene expression. Here we report a mechanism by which Twist recruits BRD4 to direct WNT5A expression in basal-like breast cancer (BLBC). Twist contains a "histone H4-mimic" GK-X-GK motif that is diacetylated by Tip60. The diacetylated Twist binds the second bromodomain of BRD4, whose first bromodomain interacts with acetylated H4, thereby constructing an activated Twist/BRD4/P-TEFb/RNA-Pol II complex at the WNT5A promoter and enhancer. Pharmacologic inhibition of the Twist-BRD4 association reduced WNT5A expression and suppressed invasion, cancer stem cell (CSC)-like properties, and tumorigenicity of BLBC cells. Our study indicates that the interaction with BRD4 is critical for the oncogenic function of Twist in BLBC.Entities:
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Year: 2014 PMID： 24525235 PMCID： PMC4004960 DOI： 10.1016/j.ccr.2014.01.028
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743