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Polycomb Group Proteins EZH2 and EED Directly Regulate Androgen Receptor in Advanced Prostate Cancer

Polycomb Group Proteins EZH2 and EED Directly Regulate Androgen Receptor in Advanced Prostate Cancer

Qipeng Liu, Guangyu Wang, Qiaqia Li, Weihua Jiang, Jung-Sun Kim, Rui Wang, Sen Zhu, Xiaoju Wang, Lin Yan, Yang Yi, Lili Zhang, Qingshu Meng, Chao Li, Dongyu Zhao, Yuanyuan Qiao, Yong Li, Demirkan B Gursel, etc.

Int J Cancer. 2019 Jul 15;145(2):415-426.

PMID: 30628724

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP68844779-A	Astemizole		68844-77-9	Price

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