@article{1176454c31fd40878179289001641f15,
title = "Polycomb group proteins EZH2 and EED directly regulate androgen receptor in advanced prostate cancer",
abstract = "Polycomb group proteins are important epigenetic regulators for cell proliferation and differentiation, organ development, as well as initiation and progression of lethal diseases, including cancer. Upregulated Polycomb group proteins, including Enhancer of zeste homolog 2 (EZH2), promote proliferation, migration, invasion and metastasis of cancer cells, as well as self-renewal of cancer stem cells. In our study, we report that EZH2 and embryonic ectoderm development (EED) indicate respective direct interaction with androgen receptor (AR). In the context of AR-positive prostate cancer, EZH2 and EED regulate AR expression levels and AR downstream targets. More importantly, we demonstrate that targeting EZH2 with the small-molecule inhibitor astemizole in cancer significantly represses the EZH2 and AR expression as well as the neoplastic capacities. These results collectively suggest that pharmacologically targeting EZH2 might be a promising strategy for advanced prostate cancer.",
keywords = "EED, EZH2, androgen receptor, astemizole, prostate cancer, Humans, Male, Gene Expression Regulation, Neoplastic/drug effects, Signal Transduction/drug effects, Xenograft Model Antitumor Assays, Enhancer of Zeste Homolog 2 Protein/metabolism, Animals, Sequence Analysis, RNA, Receptors, Androgen/genetics, Polycomb Repressive Complex 2/metabolism, Astemizole/administration & dosage, Cell Line, Tumor, Prostatic Neoplasms/drug therapy, Mice",
author = "Qipeng Liu and Guangyu Wang and Qiaqia Li and Weihua Jiang and Kim, {Jung Sun} and Rui Wang and Sen Zhu and Xiaoju Wang and Lin Yan and Yang Yi and Lili Zhang and Qingshu Meng and Chao Li and Dongyu Zhao and Yuanyuan Qiao and Yong Li and Gursel, {Demirkan B.} and Chinnaiyan, {Arul M.} and Kaifu Chen and Qi Cao",
note = "Funding Information: Key words: EZH2, EED, androgen receptor, astemizole, prostate cancer Additional Supporting Information may be found in the online version of this article. Q.L., G.W. and Q.L. contributed equally to this work Yong Li{\textquoteright}s current address is: Department of Anatomy and Biology, School of Medicine, Indiana University, Bloomington, IN Grant sponsor: NIH/NHLBI; Grant numbers: HL099997, HL100397; Grant sponsor: NIH/NCI; Grant number: R01CA208257; Grant sponsor: American Cancer Society; Grant number: TBE-128382; Grant sponsor: U.S. Department of Defense; Grant numbers: W81XWH-15-1-0639, W81XWH-17-1-0357; Grant sponsor: Prostate Cancer Foundation; Grant number: 13YOUN007; Grant sponsor: Houston Methodist Research Institute; Grant sponsor: Northwestern University DOI: 10.1002/ijc.32118 History: Received 12 Jun 2018; Accepted 19 Dec 2018; Online 10 Jan 2019 Correspondence to: Kaifu Chen, Ph.D. 6670 Bertner Ave, R10-217, Houston Methodist Research Institute, Houston, TX 77030, E-mail: kchen2@houstonmethodist.org; Tel.: (+1) 713-363-7205; or Qi Cao, Ph.D. 303 E. Chicago Ave, Tarry 16-707, Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, Tel.: +1-312-503-5990, E-mail: qi.cao@northwestern.edu Funding Information: Houston Methodist Research Institute, Prostate Cancer Foundation (13YOUN007 to Q.C.), U.S. Department of Defense (W81XWH-15-1-0639 and W81XWH-17-1-0357 to Q.C.), American Cancer Society (TBE-128382 to Q.C.), and NIH/NCI (R01CA208257 to Q.C.); K.C. is Publisher Copyright: {\textcopyright} 2019 UICC Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",
year = "2019",
month = jul,
day = "15",
doi = "10.1002/ijc.32118",
language = "English (US)",
volume = "145",
pages = "415--426",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley",
number = "2",
}