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However, the relationship between glycogenes and prostate cancer (PCa) remains poorly understood. This study aims to identify glycogenes involved in the onset and progression of PCa and to investigate the molecular mechanisms underlying their role. By integrating RNA\u2010seq data from multiple clinical cohorts (TCGA and CPGEA) and performing biochemical validation, we identified beta\u20101,4\u2010N\u2010acetylgalactosaminyltransferase 4 (B4GALNT4) as a glycogene significantly associated with advanced pathological stages, higher Gleason scores, and poor prognosis in PCa patients. Furthermore, multivariate Cox regression analysis confirmed B4GALNT4 as an independent prognostic factor for survival. Mechanistically, we discovered that B4GALNT4 interacts with PDK1 and glycosylates it at residue N531. This N\u2010glycosylation stabilizes PDK1 by blocking its degradation, thereby activating the PI3K\u2010AKT signaling pathway. This signaling axis promotes PCa cell proliferation, migration, and invasion in vitro. Moreover, B4GALNT4 knockdown suppresses tumor growth in xenograft models and correlates with decreased PDK1 and p\u2010AKT levels in vivo. Our findings establish B4GALNT4 as a critical regulator of PCa progression through PDK1 glycosylation and PI3K\u2010AKT activation, suggesting that B4GALNT4 serves as both a prognostic biomarker and a potential therapeutic target for PCa.<\/jats:p>","DOI":"10.1002\/advs.202511293","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T20:28:02Z","timestamp":1771273682000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["B4GALNT4\u2010Mediated Glycosylation of PDK1 Activates the PI3K\u2010AKT Signaling Pathway to Promote Prostate Cancer Progression"],"prefix":"10.1002","volume":"13","author":[{"given":"Shaoqin","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Urology Fujian Union Hospital Fujian Medical University  Fuzhou 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