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Recently, nonalcoholic steatohepatitis (NASH), characterized by liver steatosis, inflammation, cell injury (hepatocyte ballooning), and different stages of fibrosis, has emerged as a major catalyst for HCC. Because the STE20\u2010type kinases, MST3 and MST4, have been described as critical molecular regulators of NASH pathophysiology, we here focused on determining the relevance of these proteins in human HCC. By analyzing public datasets and in\u2010house cohorts, we found that hepatic\n                    <jats:italic>MST3<\/jats:italic>\n                    and\n                    <jats:italic>MST4<\/jats:italic>\n                    expression was positively correlated with the incidence and severity of HCC. We also found that the silencing of both MST3 and MST4, but also either of them individually, markedly suppressed the tumorigenesis of human HCC cells including attenuated proliferation, migration, invasion, and epithelial\u2010mesenchymal transition. Mechanistic investigations revealed lower activation of STAT3 signaling in MST3\/MST4\u2010deficient hepatocytes and identified GOLGA2 and STRIPAK complex as the binding partners of both MST3 and MST4. These findings reveal that MST3 and MST4 play a critical role in promoting the progression of HCC and suggest that targeting these kinases may provide a novel strategy for the treatment of liver cancer.\n                  <\/jats:p>","DOI":"10.1096\/fj.202300397rr","type":"journal-article","created":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T10:00:25Z","timestamp":1690279225000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["STE20\u2010type kinases MST3 and MST4 promote the progression of hepatocellular carcinoma: Evidence from human cell culture and expression profiling of liver biopsies"],"prefix":"10.1096","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3362-9062","authenticated-orcid":false,"given":"Mara","family":"Caputo","sequence":"first","affiliation":[{"name":"Department of Chemistry and Molecular Biology University of Gothenburg and Sahlgrenska University Hospital  Gothenburg 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