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

Gayatri D Shirolkar,Arun Dharmarajan,Sara Pasic,Janina Ee Tirnitz-Parker,John K Olynyk,Manoj K Bhat,Jully Gogoi-Tiwari

doi:10.15586/jrenhep.2018.29

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/?-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/?-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.

Highlights

Chronic liver disease (CLD) has become one of the most common causes of death globally with an estimated 1.03 million deaths per year, as reported in 2017
There is strong experimental evidence for Wnt signalling directly regulating the biology of liver progenitor cells (LPCs) and cancer stem cells (CSCs)
It has been estimated that Wnt/βcatenin signalling regulates the expression of more than 80 target genes involved in cell fate determination, development, regeneration, zonation, metabolism, fibrosis and carcinogenesis of the liver [44, 45]

Summary

Introduction

Chronic liver disease (CLD) has become one of the most common causes of death globally with an estimated 1.03 million deaths per year, as reported in 2017. There is strong experimental evidence for Wnt signalling directly regulating the biology of LPCs and CSCs. Using the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) model of chronic liver injury, Hu et al demonstrated Wnt/β-catenin signalling activity in proliferating A6+ LPCs and ductular reactions.

Results

Conclusion