| Literature DB >> 29153843 |
Shipra Shukla1, Joanna Cyrta2, Devan A Murphy1, Edward G Walczak1, Leili Ran1, Praveen Agrawal3, Yuanyuan Xie1, Yuedan Chen1, Shangqian Wang1, Yu Zhan1, Dan Li4, Elissa W P Wong1, Andrea Sboner5, Himisha Beltran6, Juan Miguel Mosquera2, Jessica Sher1, Zhen Cao1, John Wongvipat1, Richard P Koche7, Anuradha Gopalan8, Deyou Zheng9, Mark A Rubin2, Howard I Scher10, Ping Chi11, Yu Chen12.
Abstract
Prostate cancer exhibits a lineage-specific dependence on androgen signaling. Castration resistance involves reactivation of androgen signaling or activation of alternative lineage programs to bypass androgen requirement. We describe an aberrant gastrointestinal-lineage transcriptome expressed in ∼5% of primary prostate cancer that is characterized by abbreviated response to androgen-deprivation therapy and in ∼30% of castration-resistant prostate cancer. This program is governed by a transcriptional circuit consisting of HNF4G and HNF1A. Cistrome and chromatin analyses revealed that HNF4G is a pioneer factor that generates and maintains enhancer landscape at gastrointestinal-lineage genes, independent of androgen-receptor signaling. In HNF4G/HNF1A-double-negative prostate cancer, exogenous expression of HNF4G at physiologic levels recapitulates the gastrointestinal transcriptome, chromatin landscape, and leads to relative castration resistance.Entities:
Keywords: ChIP-seq; HNF1A; HNF4G; SPINK1; androgen-deprivation therapy; castration resistance; enzalutamide; pioneer factor; prostate cancer
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Year: 2017 PMID： 29153843 PMCID： PMC5728174 DOI： 10.1016/j.ccell.2017.10.008
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743