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Although fatty acid synthase (FASN) is highly expressed in PCa, the mechanisms governing FASN protein stability and its functional integration into oncogenic lipid metabolism remain poorly defined. In this study, we identified chaperonin\u2010containing TCP1 subunit 2 (CCT2) as a key oncogenic regulator that promotes lipid synthesis and enhances malignant phenotypes both in vitro and in vivo. Mechanistically, CCT2 transcription is upregulated by the transcription factor Forkhead Box A1 (FOXA1); the CCT2 protein interacts with eukaryotic translation initiation factor 3 subunit F (EIF3F) and FASN to facilitate the assembly of a CCT2\/EIF3F\/FASN ternary complex. This complex enhances the EIF3F\u2010mediated deubiquitination of FASN, increasing FASN stability and lipid synthesis, and accelerating tumor progression. Either orlistat\u2010mediated FASN inhibition or Y043\u20108015\u2010induced disruption of the CCT2\u2010EIF3F interaction effectively suppressed CCT2\u2010driven tumor progression in vivo. Importantly, combined treatment produced synergistic antitumor effects, significantly reducing tumor growth and metastatic burden across multiple in vivo models, including isograft and patient\u2010derived xenograft models. This study reveals that CCT2 promotes lipid metabolic reprogramming and tumor progression in prostate cancer by cooperating with EIF3F to stabilize FASN, highlighting the CCT2\u2010EIF3F\u2010FASN axis as a potential target for metabolic intervention.<\/jats:p>","DOI":"10.1002\/advs.75915","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:47:15Z","timestamp":1780472835000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CCT2 Promotes Prostate Cancer Progression Through EIF3F\u2010Dependent Stabilization of FASN"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6765-5816","authenticated-orcid":false,"given":"Shun","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Urology, the First Affiliated Hospital of Anhui Medical University Anhui Medical University  Hefei Anhui China"},{"name":"Institute of Urology Anhui Medical 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