Hepatocyte plasticity is regulated by Yap and Sox9 in liver tumor

Primary liver tumors contain a spectrum of heterogeneous subtypes with different histological features: Hepatocellular carcinoma (HCC), combined hepatocellular carcinoma-intrahepatic cholangiocarcinoma(cHCC-ICC), and intrahepatic cholangiocarcinoma (ICC). A subset of ICCs has been shown to arise directly from cell fate reprogramming of mature hepatocytes in mouse models. However, the underpinning of hepatocyte fate reprogramming or plasticity is still poorly understood, hampering therapeutic development to treat HCC and ICC. It is known that Yap activation induces tumor formation in the liver with high cell fate plasticity that involves dedifferentiation of mature hepatocytes to liver progenitor cells (LPCs) and differentiation of biliary epithelial cell (BEC)-like cells. Here we investigated the role of Sox9, a transcription factor expressed in both LPCs and BECs, in Yap-induced cell fate plasticity during liver tumor formation.