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However, the underlying molecular drivers remain largely elusive. In this study, we demonstrate that Tribbles homolog 1 (TRIB1) is elevated in PDAC tissues and is significantly associated with poor prognosis. Functionally, TRIB1 mRNA knockdown suppresses PDAC cell growth and tumor formation, while its overexpression promotes both. Mechanistically, TRIB1 protein binds to the DNA\u2010binding domain of PPAR\u03b3 and inhibits its transcriptional activity. This interaction relieves the PPAR\u03b3\u2010mediated repression of\n                    <jats:italic>HMGCR<\/jats:italic>\n                    , the rate\u2010limiting enzyme in the mevalonate pathway, thereby fueling de novo cholesterol biosynthesis. Furthermore, in vivo experiments indicate that PDAC tumors with high TRIB1 expression were more sensitive to the HMGCR inhibitor atorvastatin. Collectively, our findings highlight the critical role of the TRIB1\u2013PPAR\u03b3\u2013HMGCR axis in the metabolic rewiring of PDAC and suggest that TRIB1 may serve as a predictive biomarker for optimizing statin\u2010based metabolic therapies.\n                  <\/jats:p>","DOI":"10.1111\/nyas.70224","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:00:51Z","timestamp":1772989251000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The TRIB1\u2013PPAR\u03b3 Axis Regulates Cholesterol Metabolism in Pancreatic Ductal Adenocarcinoma"],"prefix":"10.1111","volume":"1557","author":[{"given":"Rui","family":"Sun","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Dalian Medical University  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henan","family":"Qin","sequence":"additional","affiliation":[{"name":"The First Affiliated 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