β-catenin deficiency in hepatocytes aggravates hepatocarcinogenesis driven by oncogenic β-catenin and MET.

ABSTRACT: Both activating and inactivating mutations in catenin β1 (ctnnb1), which encodes β-catenin, have been implicated in liver tumorigenesis in humans and mice, although the underlying mechanisms are not fully understood. Herein, we show that deletion of endogenous β-catenin in hepatocytes aggravated hepatocellular carcinoma (HCC) development driven by an oncogenic version of β-catenin (CAT) in combination with the hepatocyte growth factor receptor MET proto-oncogene receptor tyrosine kinase (MET). Although the mitogenic signaling and cell cycle progression was modestly impaired after CAT/MET transfection, the β-catenin-deficient livers displayed changes in transcriptomes, increased DNA damage response, expanded Sox9⁺ cells, and up-regulation of protumorigenic cytokines, including in

SUBMITTER: Liang Y 

PROVIDER: S-EPMC5906147 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature