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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,3,25]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic>ETV5<\/jats:italic>\n                    expression compared to other subtypes. ETV5 expression increased progressively under hormone therapy through epigenetic modifications. ETV5 induced neural stem\u2013like 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\n                    <jats:italic>PBX3<\/jats:italic>\n                    and\n                    <jats:italic>TLL1<\/jats:italic>\n                    as target genes of ETV5 that contribute to ETV5 overexpression\u2013induced 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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2420313122","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T13:40:27Z","timestamp":1742564427000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":8,"title":["ETV5 reduces androgen receptor expression and induces neural stem\u2013like properties during neuroendocrine prostate cancer development"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4668-2329","authenticated-orcid":false,"given":"Jongeun","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology","place":["Pohang, Gyeongbuk, Republic of 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Gyeongbuk, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeon-Soo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology","place":["Pohang, Gyeongbuk, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4072-3807","authenticated-orcid":false,"given":"Kyuha","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Pohang University of Science and Technology","place":["Pohang, Gyeongbuk, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunjeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Natural Sciences, Kyungpook National University","place":["Daegu, Republic of 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Qi , Function and regulation of the PEA3 subfamily of ETS transcription factors in cancer. Am. J. Cancer Res. 10, 3083\u20133105 (2020).","journal-title":"Am. J. Cancer Res."},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-1230-7"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms16037"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2322009121"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16083"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41417-020-00239-8"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-12629-4"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16071368"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-023-09106-9"},{"key":"e_1_3_4_60_2","unstructured":"J. Lee Data from \u201cETV5 reduces androgen receptor expression and induces neural stem-like properties during neuroendocrine prostate cancer development.\u201d Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE271776. Deposited 8 July 2024."},{"key":"e_1_3_4_61_2","unstructured":"J. Lee Data from \u201cETV5 reduces androgen receptor expression and induces neural stem-like properties during neuroendocrine prostate cancer development.\u201d Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE271777. 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