Wnt/?-Catenin Signalling during Liver Metabolism, Chronic Liver Disease and Hepatocarcinogenesis

Abstract

Chronic liver diseases (CLDs) are increasing in prevalence and their end-stage complications, namely, cirrhosis, liver failure and hepatocellular carcinoma represent major global challenges. The most common initiators of progressive CLD are viral hepatitis and long-term alcohol abuse as well as steatosis and steatohepatitis. Irrespective of the underlying aetiology, a common feature of CLD is the formation of hepatic ductular reactions, involving the proliferation of liver progenitor cells (LPCs) and their signalling to fibrosis-driving hepatic stellate cells. The Wnt/β-catenin pathway has been found to regulate development, stemness and differentiation, and alterations in its activity have been associated with tumour development. Recent data highlight the role of Wnt/β-catenin signalling in hepatic metabolism, steatosis and cancer, and suggest targeting of this pathway as a promising molecular strategy to potentially inhibit CLD progression and hepatocarcinogenesis.

Mouse Models of Hepatocellular Carcinoma

“…Wnt/β-catenin signaling controls a plethora of cellular communication networks in embryonic development and demonstrates key roles in regulating stemness and cell differentiation in health and disease (118). Pathological alterations of this pathway are known for its involvement in many human cancers, including liver cancer (118,119). Beta-catenin is one of the key effectors of Wnt signaling, and its gene CTNNB1 is the most frequently found mutated component of this pathway in human HCC (120).…”