LKB1 signaling is activated in CTNNB1-mutated HCC and positively regulates β-catenin-dependent CTNNB1-mutated HCC.

Hepatocellular carcinomas (HCCs) are known to be highly heterogenous. Within the extensive histopathological and molecular heterogeneity of HCC, tumors with mutations in CTNNB1, encoding β-catenin (CTNNB1-mutated HCC), constitute a very homogeneous group. We previously characterized a distinctive metabolic and histological phenotype for CTNNB1-mutated HCC.

AXIN deficiency in human and mouse hepatocytes induces hepatocellular carcinoma in the absence of β-catenin activation.

Background & Aims: The Wnt/β-catenin pathway is the most frequently deregulated pathway in hepatocellular carcinoma (HCC). Inactivating mutations of the gene encoding AXIN1, a known negative regulator of the Wnt/β-catenin signaling pathway, are observed in about 10% of HCCs. Whole-genome studies usually place HCC with AXIN1 mutations and CTNNB1 mutations in the group of tumors with Wnt/β-catenin activated program.