ETV5 reduces androgen receptor expression and induces neural stem–like properties during neuroendocrine prostate cancer development

IF 9.4 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-03-21 DOI:10.1073/pnas.2420313122

Jongeun Lee, Jiho Park, Yunjung Hur, Dahun Um, Hyung-Seok Choi, Joonyoung Park, Yewon Kim, Jeon-Soo Lee, Kyuha Choi, Eunjeong Kim, Young Bin Park, Jae-Mun Choi, Tae-Kyung Kim, Yoontae Lee

{"title":"ETV5 reduces androgen receptor expression and induces neural stem–like properties during neuroendocrine prostate cancer development","authors":"Jongeun Lee, Jiho Park, Yunjung Hur, Dahun Um, Hyung-Seok Choi, Joonyoung Park, Yewon Kim, Jeon-Soo Lee, Kyuha Choi, Eunjeong Kim, Young Bin Park, Jae-Mun Choi, Tae-Kyung Kim, Yoontae Lee","doi":"10.1073/pnas.2420313122","DOIUrl":null,"url":null,"abstract":"Neuroendocrine prostate cancer (NEPC), an aggressive subtype induced by hormone therapy, lacks effective treatments. This study explored the role of E26 transformation-specific variant 5 (ETV5) in NEPC development. Analysis of multiple prostate cancer datasets revealed that NEPC is characterized by significantly elevated ETV5 expression compared to other subtypes. ETV5 expression increased progressively under hormone therapy through epigenetic modifications. ETV5 induced neural stem–like features in prostate cancer cells and facilitated their differentiation into NEPC under hormone treatment conditions, both in vitro and in vivo. Our molecular mechanistic study identified PBX3 and TLL1 as target genes of ETV5 that contribute to ETV5 overexpression–induced castration resistance and stemness. Notably, obeticholic acid, identified as an ETV5 inhibitor in this study, exhibited promising efficacy in suppressing NEPC development. This study highlights ETV5 as a key transcription factor that facilitates NEPC development and underscores its potential as a therapeutic target for this aggressive cancer subtype.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"27 1","pages":""},"PeriodicalIF":9.4000,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Proceedings of the National Academy of Sciences of the United States of America","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1073/pnas.2420313122","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Neuroendocrine prostate cancer (NEPC), an aggressive subtype induced by hormone therapy, lacks effective treatments. This study explored the role of E26 transformation-specific variant 5 (ETV5) in NEPC development. Analysis of multiple prostate cancer datasets revealed that NEPC is characterized by significantly elevated ETV5 expression compared to other subtypes. ETV5 expression increased progressively under hormone therapy through epigenetic modifications. ETV5 induced neural stem–like features in prostate cancer cells and facilitated their differentiation into NEPC under hormone treatment conditions, both in vitro and in vivo. Our molecular mechanistic study identified PBX3 and TLL1 as target genes of ETV5 that contribute to ETV5 overexpression–induced castration resistance and stemness. Notably, obeticholic acid, identified as an ETV5 inhibitor in this study, exhibited promising efficacy in suppressing NEPC development. This study highlights ETV5 as a key transcription factor that facilitates NEPC development and underscores its potential as a therapeutic target for this aggressive cancer subtype.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Proceedings of the National Academy of Sciences of the United States of America 综合性期刊-综合性期刊

CiteScore

19.00

自引率

0.90%

发文量

3575

审稿时长

2.5 months

期刊介绍： The Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed journal of the National Academy of Sciences (NAS), serves as an authoritative source for high-impact, original research across the biological, physical, and social sciences. With a global scope, the journal welcomes submissions from researchers worldwide, making it an inclusive platform for advancing scientific knowledge.