@article{485f96431a43456997fe422fb5c7ba30,
title = "Disrupting the Interaction of BRD4 with Diacetylated Twist Suppresses Tumorigenesis in Basal-like Breast Cancer",
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.",
author = "Jian Shi and Yifan Wang and Lei Zeng and Yadi Wu and Jiong Deng and Qiang Zhang and Yiwei Lin and Junlin Li and Tiebang Kang and Min Tao and Elena Rusinova and Guangtao Zhang and Chi Wang and Haining Zhu and Jun Yao and Zeng, \{Yi Xin\} and Evers, \{B. Mark\} and Zhou, \{Ming Ming\} and Zhou, \{Binhua P.\}",
note = "Funding Information: We thank Cathy Anthony for critical reading and editing of this manuscript. We also thank Dr. Jing Chen for technical assistance on mass spectrometry analysis. We are grateful to Dr. James E. Bradner for providing JQ1, Dr. Robert A. Weinberg for HMLE cells, Dr. Michael Rosenblatt for SUM1315 cells, and Dr. Bruno Amati for Tip60 antibodies as valuable reagents for this study. This work was supported in part by grants from the National Institute of Health (CA125454 to B.P.Z., P20CA153043 to B.M.E., and HG004508 and CA87658 to M.-M.Z.), the American Cancer Society (RSG13187 to Y.W.), and the Nature Science Foundation of China (91129303 to J.D.). We acknowledge the University of Kentucky Proteomics Core, which is partially supported by grants from the National Cancer Institute (P30CA177558) and the National Institute of General Medical Sciences (P20GM103486). ",
year = "2014",
month = feb,
day = "10",
doi = "10.1016/j.ccr.2014.01.028",
language = "English (US)",
volume = "25",
pages = "210--225",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",
}