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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 12, 2019
- Source ID
- 10.1002/ijc.32118
Entities
People
- Arul Chinnaiyan
- Chao Li
- Demirkan B. Gursel
- Dongyu Zhao
- Guangyu Wang
- Jung‐sun Kim
- Kaifu Chen
- Lili Zhang
- Lin Yan
- Qi Cao
- Qiaqia Li
- Qingshu Meng
- Qipeng Liu
- Rui Wang
- Sen Zhu
- Weihua Jiang
- Xiaoju Wang
- Yi Yang
- Yong Li
- Yuanyuan Qiao
Organizations
- American Cancer Society
- Central South University
- Cornell University
- Houston Methodist Hospital
- National Heart, Lung, and Blood Institute
- Northwestern University
- Prostate Cancer Foundation
- Sun Yat-sen University
- United States Department of Defense
- University of Michigan