Hepatic zonation determines tumorigenic potential of mutant β-catenin.

ABSTRACT: Oncogenic mutations in phenotypically normal tissue are common across adult organs^1,2. This suggests that multiple events need to converge to drive tumorigenesis and that many processes such as tissue differentiation may protect against carcinogenesis. WNT-β-catenin signalling maintains zonal differentiation during liver homeostasis^3,4. However, the CTNNB1 oncogene-encoding β-catenin-is also frequently mutated in hepatocellular carcinoma, resulting in aberrant WNT signalling that promotes cell growth^5,6. Here we investigated the antagonistic interplay between WNT-driven growth and differentiation in zonal hepatocyte populations during liver tumorigenesis. We found that β-catenin mutations co-operate with exogenous MYC expression to drive a proliferative tra

SUBMITTER: Raven A 

PROVIDER: S-EPMC12804091 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature