| Literature DB >> 28916652 |
Yi Liang1, Musaddeque Ahmed1, Haiyang Guo1, Fraser Soares1, Junjie T Hua1,2, Shuai Gao3, Catherine Lu1, Christine Poon1, Wanting Han3, Jens Langstein1,4, Muhammad B Ekram5,6,7, Brian Li1, Elai Davicioni8, Mandeep Takhar8, Nicholas Erho8, R Jeffrey Karnes9, Dianne Chadwick10, Theodorus van der Kwast11, Paul C Boutros2,12,13, Cheryl H Arrowsmith1,14, Felix Y Feng15,16,17,18, Anthony M Joshua1,19, Amina Zoubeidi20, Changmeng Cai3, Housheng H He21,2.
Abstract
Androgen receptor (AR) signaling is a key driver of prostate cancer, and androgen-deprivation therapy (ADT) is a standard treatment for patients with advanced and metastatic disease. However, patients receiving ADT eventually develop incurable castration-resistant prostate cancer (CRPC). Here, we report that the chromatin modifier LSD1, an important regulator of AR transcriptional activity, undergoes epigenetic reprogramming in CRPC. LSD1 reprogramming in this setting activated a subset of cell-cycle genes, including CENPE, a centromere binding protein and mitotic kinesin. CENPE was regulated by the co-binding of LSD1 and AR to its promoter, which was associated with loss of RB1 in CRPC. Notably, genetic deletion or pharmacological inhibition of CENPE significantly decreases tumor growth. Our findings show how LSD1-mediated epigenetic reprogramming drives CRPC, and they offer a mechanistic rationale for its therapeutic targeting in this disease. Cancer Res; 77(20); 5479-90. ©2017 AACR. ©2017 American Association for Cancer Research.Entities:
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Year: 2017 PMID： 28916652 DOI： 10.1158/0008-5472.CAN-17-0496
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701