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The mechanisms of branched-chain amino acids (BCAAs) contributing to the development of PCa remain inadequately elucidated. The objective of this study was to examine the involvement of BCAAs and BCAT2 in tumorigenesis. BCAAs exhibited elevated expression levels in PCa tissues and cells. Among the critical enzymes involved in the BCAA metabolic pathway, only BCAT2 demonstrated significant expression in PCa and was closely associated with tumor progression and patient prognosis. RNA sequencing along with related functional experiments indicated that BCAT2 can inhibit autophagy, autophagy-related apoptosis, and ferroptosis in PCa. Furthermore, the results of co-immunoprecipitation, mass spectrometry, and other methodologies established that PCBP1, as a downstream protein interacting with BCAT2, co-regulates the PI3K\/AKT pathway, thereby influencing progression of PCa. Moreover, BCAT2 interacted with PCBP1 at Leucine 239 to collaboratively regulate the PI3K\/AKT signaling pathway, which is crucial for the initiation and progression of PCa. Targeting BCAT2 may represent a promising therapeutic strategy to prevent proliferation of PCa.<\/jats:p>","DOI":"10.1038\/s41419-025-07559-3","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T12:34:29Z","timestamp":1745498069000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["BCAT2 binding to PCBP1 regulates the PI3K\/AKT signaling pathway to inhibit autophagy-related apoptosis and ferroptosis in prostate cancer"],"prefix":"10.1038","volume":"16","author":[{"given":"Wangli","family":"Mei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyu","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaozhi","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6015-8665","authenticated-orcid":false,"given":"Shiyong","family":"Xin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiguo","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3304-4558","authenticated-orcid":false,"given":"Lin","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"7559_CR1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3322\/caac.21820","volume":"74","author":"RL Siegel","year":"2024","unstructured":"Siegel RL, Giaquinto AN, Jemal A. 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The use of clinical specimens was approved by the Ethics Committee of Shanghai East Hospital Affiliated to Tongji University (approval number: 2024YS-244).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"337"}}