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Caputo, M.* ; Xia, Y.* ; Anand, S.K.* ; Cansby, E.* ; Andersson, E.* ; Marschall, H.U.* ; Königsrainer, A.* ; Peter, A. ; Mahlapuu, M.*

STE20-type kinases MST3 and MST4 promote the progression of hepatocellular carcinoma: Evidence from human cell culture and expression profiling of liver biopsies.

FASEB J. 37:e23105 (2023)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Hepatocellular carcinoma (HCC) is one of the most fatal and fastest growing malignancies. 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-type 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-house cohorts, we found that hepatic MST3 and MST4 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-mesenchymal transition. Mechanistic investigations revealed lower activation of STAT3 signaling in MST3/MST4-deficient 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Mst3 ; Mst4 ; Ste20-type Kinases ; Hepatocellular Carcinoma ; Hepatocellular Lipid Droplets ; Nonalcoholic Steatohepatitis; Epithelial-mesenchymal Transition; Compensatory Proliferation; Oxidative Stress; Cancer; Activation; Metastasis; Phosphorylation; Migration; Transplantation; Steatohepatitis
ISSN (print) / ISBN 0892-6638
e-ISSN 1530-6860
Zeitschrift FASEB Journal
Quellenangaben Band: 37, Heft: 8, Seiten: , Artikelnummer: e23105 Supplement: ,
Verlag Wiley
Verlagsort Bethesda, Md.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
Förderungen IngaBritt och Arne
Hjaert-Lungfonden (Swedish Heart -Lung Foundation)
Diabetesfonden (Swedish Diabetes Foundation)
Cancerfonden (Swedish Cancer Society)
Adlerbertska Stiftelserna (Adlerbertska Foundations)
Ake Wiberg Stiftelse (Ake Wiberg Foundation)