Dysregulated YAP1/TAZ and TGF-β signaling mediate hepatocarcinogenesis in Mob1a/1b -deficient mice
Copyright policy )Dysregulated YAP1/TAZ and TGF-β signaling mediate hepatocarcinogenesis in Mob1a/1b -deficient mice
Significance Patients with intrahepatic cholangiocellular carcinoma (ICC) and combined hepatocellular and cholangiocarcinoma (cHC-CC) have worse prognoses than those with hepatocellular carcinoma and rarely show clinical responses to drugs. Our analyses of mice with liver-specific deletions of Mps One Binder Kinase Activator (MOB)1A/1B reveal that MOB1A/1B constitute the most important hub of Hippo signaling in mammalian liver. MOB1A/1B maintain hepatocyte stem/progenitor cell quiescence and are potent tumor suppressors, especially in cHC-CCs and ICCs. Because these functions depend on the Hippo target Yap1 / Taz and the Yap1/Taz targets Tgfb s, our data point to a new therapeutic approach for liver cancer based on inhibition of MOB1-YAP1/TAZ and/or TGF-βs–SMADs signaling. Our demonstration that well-tolerated and already-approved antiparasitic drugs inhibit YAP1 signaling may point to a new route of treatment for these cancers that can be rapidly tested and implemented.
Mice, Knockout, Epithelial-Mesenchymal Transition, Hyperplasia, Carcinogenesis, Liver Neoplasms, Connective Tissue Growth Factor, Intracellular Signaling Peptides and Proteins, Mice, Nude, Phosphoproteins, Cholangiocarcinoma, Mice, Bile Duct Neoplasms, Liver, Cell Line, Tumor, Animals, Humans, Genes, Tumor Suppressor, Protein Kinases, Acyltransferases, Adaptor Proteins, Signal Transducing
Mice, Knockout, Epithelial-Mesenchymal Transition, Hyperplasia, Carcinogenesis, Liver Neoplasms, Connective Tissue Growth Factor, Intracellular Signaling Peptides and Proteins, Mice, Nude, Phosphoproteins, Cholangiocarcinoma, Mice, Bile Duct Neoplasms, Liver, Cell Line, Tumor, Animals, Humans, Genes, Tumor Suppressor, Protein Kinases, Acyltransferases, Adaptor Proteins, Signal Transducing
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