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Fibroblast growth factor 9 (FGF9)\u00a0is involved in serial types of cancer; however, the specific role of FGF9 in NASH\u2010driven HCC is not fully understood. This study finds that FGF9 is increased in patients with NASH\u2010associated HCC. Furthermore, NASH\u2010driven HCC mice models by feeding wildtype mice with high\u2010fat\/high\u2010cholesterol (HFHC) diet and low dose carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    ) treatment is established; and identified that hepatic FGF9 is increased; with severe fibrosis. Additionally, AAV\u2010mediated knockdown of FGF9 reduced the hepatic tumor burden of NASH\u2010driven HCC mice models. Hepatocyte\u2010specific FGF9 transgenic mice (FGF9\n                    <jats:sup>Alb<\/jats:sup>\n                    ) fed with a HFHC diet without CCl\n                    <jats:sub>4<\/jats:sub>\n                    treatment exhibited an increased hepatic ECM and tumor burden. However, XAV\u2010939 treatment blocked ECM accumulation and NASH\u2010driven HCC in FGF9\n                    <jats:sup>Alb<\/jats:sup>\n                    mice fed with HFHC diet. Molecular mechanism studies show that FGF9 stimulated the expression of ECM related genes in a \u03b2\u2010catenin dependent manner; and FGF9 exerts its effect on \u03b2\u2010catenin stability via the ERK1\/2\u2010GSK\u20103\u03b2 signaling pathway. In summary, the data provides evidence for the critical role of FGF9 in NASH\u2010driven HCC pathogenesis; wherein it promotes the tumors formation through the ECM pathway.\n                  <\/jats:p>","DOI":"10.1002\/advs.202301166","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T15:27:06Z","timestamp":1691767626000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["FGF9 Recruits \u03b2\u2010Catenin to Increase Hepatic ECM Synthesis and Promote NASH\u2010Driven HCC"],"prefix":"10.1002","volume":"10","author":[{"given":"Lei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Metabolic Disease Research Center School of Basic Medicine Anhui Medical University  230032 Hefei China"},{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) Tianjin Key of Cellular Homeostasis and Disease 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