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Polycomb group proteins EZH2 and EED directly regulate androgen receptor in advanced prostate cancer
Author(s) -
Liu Qipeng,
Wang Guangyu,
Li Qiaqia,
Jiang Weihua,
Kim JungSun,
Wang Rui,
Zhu Sen,
Wang Xiaoju,
Yan Lin,
Yi Yang,
Zhang Lili,
Meng Qingshu,
Li Chao,
Zhao Dongyu,
Qiao Yuanyuan,
Li Yong,
Gursel Demirkan B.,
Chinnaiyan Arul M.,
Chen Kaifu,
Cao Qi
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32118
Subject(s) - prostate cancer , androgen receptor , ezh2 , cancer research , polycomb group proteins , androgen , biology , medicine , chemistry , cancer , oncology , epigenetics , genetics , repressor , transcription factor , hormone , gene
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.