| Literature DB >> 35617398 |
Fanying Tang1,2, Duo Xu1,2,3,4, Shangqian Wang5,6, Chen Khuan Wong5, Alexander Martinez-Fundichely1,2,3,4, Cindy J Lee5, Sandra Cohen1, Jane Park7, Corinne E Hill7, Kenneth Eng4, Rohan Bareja4, Teng Han5, Eric Minwei Liu1,2,8, Ann Palladino1,2, Wei Di5, Dong Gao5,9, Wassim Abida10, Shaham Beg4, Loredana Puca1,4, Maximiliano Meneses11, Elisa de Stanchina11, Michael F Berger12, Anuradha Gopalan12, Lukas E Dow1,13, Juan Miguel Mosquera1,4,14, Himisha Beltran4,15, Cora N Sternberg1,4, Ping Chi5,10,13, Howard I Scher10,16, Andrea Sboner2,4,14, Yu Chen5,10,13, Ekta Khurana1,2,3,4.
Abstract
In castration-resistant prostate cancer (CRPC), the loss of androgen receptor (AR) dependence leads to clinically aggressive tumors with few therapeutic options. We used ATAC-seq (assay for transposase-accessible chromatin sequencing), RNA-seq, and DNA sequencing to investigate 22 organoids, six patient-derived xenografts, and 12 cell lines. We identified the well-characterized AR-dependent and neuroendocrine subtypes, as well as two AR-negative/low groups: a Wnt-dependent subtype, and a stem cell-like (SCL) subtype driven by activator protein-1 (AP-1) transcription factors. We used transcriptomic signatures to classify 366 patients, which showed that SCL is the second most common subtype of CRPC after AR-dependent. Our data suggest that AP-1 interacts with the YAP/TAZ and TEAD proteins to maintain subtype-specific chromatin accessibility and transcriptomic landscapes in this group. Together, this molecular classification reveals drug targets and can potentially guide therapeutic decisions.Entities:
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Year: 2022 PMID： 35617398 PMCID： PMC9299269 DOI： 10.1126/science.abe1505
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 63.714