{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Li H"],"funding":["Qian De Young Talent Nurturing Project","China Postdoctoral Science Foundation","National Natural Science Foundation of China","Science-Health Joint Medical Scientific Research Project of Chongqing","General Project of Chongqing Natural Science Foundation","Graduate Tutor Team Construction Project of Chongqing Medical University","Chongqing Postdoctoral Science Foundation"],"pagination":["e09769"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12713097"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(47)"],"pubmed_abstract":["The molecular mechanisms of estrogen receptor α (ERα)-positive breast carcinogenesis and endocrine resistance remain unclear. This study identifies ADP-ribosylation factor-like protein 3 (ARL3) as a key oncogenic regulator overexpressed in ERα-positive breast cancer cells and tissues. Mechanistically, ARL3 stabilizes ERα as a novel chaperone via direct binding, enhancing ESR1-driven transcription and cell proliferation. Genetic ablation of ARL3 induces ERα ubiquitination-dependent degradation, activating mTOR/AMPK pathways and causing mitophagy/mitochondrial dysfunction. ARL3 maintains ERα stability by upregulating USP10, which removes K48/K63-linked polyubiquitin chains from ERα at the K252 site. In preclinical models, the small-molecule inhibitor A-1331852 (targeting ARL3) potently suppr"],"journal":["Advanced science (Weinheim, Baden-Wurttemberg, Germany)"],"pubmed_title":["ARL3 Enhances ERα Stability via USP10 Deubiquitination to Promote Endocrine Resistance and Drive Mitochondrial Metabolic Reprogramming in HR+ Breast Cancer."],"pmcid":["PMC12713097"],"funding_grant_id":["82403086","cqmudstd202212","CSTB2023NSCQ-BHX0023","2025QDPY-02","2023MD734130","CSTB2025NSCQ-GPX1151","2025DBXM005"],"pubmed_authors":["Shen M","Li H","Peng Y","Lan A","Shu D","He K","Guo S","Liu S","Li K","Yu H","Liu X","Liu Y","Jin A","Cai Z","Gao S"],"additional_accession":[]},"is_claimable":false,"name":"ARL3 Enhances ERα Stability via USP10 Deubiquitination to Promote Endocrine Resistance and Drive Mitochondrial Metabolic Reprogramming in HR+ Breast Cancer.","description":"The molecular mechanisms of estrogen receptor α (ERα)-positive breast carcinogenesis and endocrine resistance remain unclear. This study identifies ADP-ribosylation factor-like protein 3 (ARL3) as a key oncogenic regulator overexpressed in ERα-positive breast cancer cells and tissues. Mechanistically, ARL3 stabilizes ERα as a novel chaperone via direct binding, enhancing ESR1-driven transcription and cell proliferation. Genetic ablation of ARL3 induces ERα ubiquitination-dependent degradation, activating mTOR/AMPK pathways and causing mitophagy/mitochondrial dysfunction. ARL3 maintains ERα stability by upregulating USP10, which removes K48/K63-linked polyubiquitin chains from ERα at the K252 site. In preclinical models, the small-molecule inhibitor A-1331852 (targeting ARL3) potently suppr","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-06-06T04:31:16.371Z","creation":"2026-05-25T03:11:43.041Z"},"accession":"S-EPMC12713097","cross_references":{"pubmed":["41047477"],"doi":["10.1002/advs.202509769"]}}