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Despite the tumor\u2010suppressive role of lactoferrin established in other malignancies, we reveal its paradoxical oncogenic function in prostate cancer through an androgen receptor (AR)\u2010LF\u2010ferroptosis axis. Utilizing\n                    <jats:italic>\n                      Lf\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    TRAMP genetic mouse models, proteomics, TCGA\u2010PARD data, and single\u2010cell RNA\u2010seq, we demonstrate that AR directly binds the\n                    <jats:italic>LF<\/jats:italic>\n                    promoter, driving\n                    <jats:italic>LF<\/jats:italic>\n                    expression, which in turn upregulates ferritin (FTH1\/FTL) expression and suppresses p53\u2010ALOX12\u2010mediated ferroptosis in prostate cancer. Crucially,\n                    <jats:italic>Lf<\/jats:italic>\n                    deficiency delayed tumor progression and intensified ferroptotic stress in the TRAMP mice, while iron supplementation accelerated carcinogenesis\u2014effects rescued by\n                    <jats:italic>Lf<\/jats:italic>\n                    knockout. Mechanistically, lactoferrin shields prostate cancer cells from iron\u2010induced ferroptosis by maintaining iron\u2010redox homeostasis. Preclinical targeting of this axis suggested a potential therapeutic strategy, as suppressed tumor growth in prostate cancer xenograft was observed following\n                    <jats:italic>LF<\/jats:italic>\n                    knockdown coupled with ferroptosis induction (via IKE) and androgen receptor inhibition (via enzalutamide). This work defines lactoferrin as: (i) an AR\u2010regulated ferroptosis suppressor, (ii) a regulator of prostate cancer's \u201ciron addiction,\u201d and (iii) a candidate target for therapeutic exploitation of iron\u2010metabolic vulnerability.\n                  <\/jats:p>","DOI":"10.1002\/advs.202520109","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T19:49:34Z","timestamp":1775591374000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Androgen Receptor\u2010Induced Lactoferrin Accelerates Prostate Tumorigenesis Through Modulating Ferroptosis"],"prefix":"10.1002","volume":"13","author":[{"given":"Can","family":"Liu","sequence":"first","affiliation":[{"name":"Hunan Key Laboratory of Cancer Metabolism Hunan Cancer Hospital\/ The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Changsha Hunan China"},{"name":"Cancer Research Institute Xiangya 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