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Here, CCT6A is identified as a CAF\u2010derived factor whose high expression is positively associated with GC progression and plays a key regulatory role in stemness, chemoresistance, and glucose metabolism. In a co\u2010culture system of CAFs and cancer cells, it is discovered that CCT6A is transferred from CAFs to tumor cells mainly via exosomal transport, thereby enhancing stemness, chemoresistance, and glycolysis. Mechanistically, CCT6A interacts with \u03b2\u2010catenin, inducing its phosphorylation and nuclear translocation, which subsequently leads to transcriptional suppression of the glycolysis inhibitors DDIT4 and TXNIP through c\u2010Myc activation. Furthermore, a feedforward regulatory loop is uncovered in which the CCT6A pseudogene CCT6P1 acts as a competitive endogenous RNA (ceRNA) by sequestering miR\u2010922, thereby stabilizing CCT6A expression, while c\u2010Myc co\u2010activates both CCT6A and CCT6P1, amplifying oncogenic signaling. Collectively, the findings not only reveal the pivotal mediator of CAF\u2010secreted CCT6A in orchestrating stemness, chemoresistance, and metabolic reprogramming in GC but also highlight its dual utility as a diagnostic biomarker and therapeutic target.<\/jats:p>","DOI":"10.1002\/advs.202506674","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T12:17:16Z","timestamp":1755087436000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Exosomal CCT6A Secreted by Cancer\u2010Associated Fibroblasts Interacts with \u03b2\u2010Catenin to Enhance Chemoresistance and Tumorigenesis in Gastric Cancer"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7145-6991","authenticated-orcid":false,"given":"Hui","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Pathology Fudan University Shanghai Cancer Center  Shanghai 200032 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