PD59-01 INSM1 IS A DRIVER OF NEUROENDOCRINE PROSTATE CANCER

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology III (PD59)1 Apr 2020PD59-01 INSM1 IS A DRIVER OF NEUROENDOCRINE PROSTATE CANCER Zhixiang Xin*, Jiahua Pan, Baijun Dong, and Wei Xue Zhixiang Xin*Zhixiang Xin* More articles by this author , Jiahua PanJiahua Pan More articles by this author , Baijun DongBaijun Dong More articles by this author , and Wei XueWei Xue More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000969.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Neuroendocrine prostate cancer (NEPC), arising mostly from adenocarcinoma via NE transdifferentiation following androgen deprivation therapy, is a lethal subtype of prostate cancer (PCa). Mechanisms contributing to NEPC development and its aggressiveness remain elusive. We previously reported that INSM1 is a novel sensitive marker for NEPC. We hypotheses that INSM1 involved in the NE transdifferentiation of prostate cancer. METHODS: Pan-neuroendocrine tumor database was reviewed. Patient-derived xenograft (PDX) models, clinical cohorts, cell lines and genetically engineered mouse models (Pbcre4 Rb1-/-TP53-/-) were utilized. RESULTS: Here, through pan-neuroendocrine tumor analyses, we identified INSM1 as a candidate master transcriptional regulator of poorly differentiated NEPC. Transcriptomic analyses of our patient-derived xenograft (PDX) models, clinical cohorts, cell lines and genetically engineered mouse models (Pbcre4 Rb1-/-TP53-/-) confirmed INSM1 is significantly enriched in NEPC. INSM1 knockdown in the NCI-H660 NEPC cell line inhibited proliferation, ablated colony formation, ultimately leading to tumor growth arrest. This result was further confirmed in organoids derived from genetically engineered mouse tumor tissues. INSM1 ectopic expression significantly promoted NE transdifferentiation in adenocarcinoma cells LNCAP subjected to androgen deprivation treatment. Mechanistically, INSM1 binded to the Hes1 promoter and represses Hes1. CONCLUSIONS: Collectively, these observations highlight the role of INSM1 in driving NEPC, and emphasize the potential therapeutic target for NEPC. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1205-e1205 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Zhixiang Xin* More articles by this author Jiahua Pan More articles by this author Baijun Dong More articles by this author Wei Xue More articles by this author Expand All Advertisement PDF downloadLoading ...