Wnt-β-catenin signalling in liver development, health and disease.

Abstract

The canonical Wnt-β-catenin pathway is a complex, evolutionarily conserved signalling mechanism that regulates fundamental physiological and pathological processes. Wnt-β-catenin signalling tightly controls embryogenesis, including hepatobiliary development, maturation and zonation. In the mature healthy liver, the Wnt-β-catenin pathway is mostly inactive but can become re-activated during cell renewal and/or regenerative processes, as well as in certain pathological conditions, diseases, pre-malignant conditions and cancer. In hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), the two most prevalent primary liver tumours in adults, Wnt-β-catenin signalling is frequently hyperactivated and promotes tumour growth and dissemination. A substantial proportion of liver tumours (mainly HCC and, to a lesser extent, CCA) have mutations in genes encoding key components of the Wnt-β-catenin signalling pathway. Likewise, hepatoblastoma, the most common paediatric liver cancer, is characterized by Wnt-β-catenin activation, mostly as a result of β-catenin mutations. In this Review, we discuss the most relevant molecular mechanisms of action and regulation of Wnt-β-catenin signalling in liver development and pathophysiology. Moreover, we highlight important preclinical and clinical studies and future directions in basic and clinical research.

• Authors: Maria J Perugorria, Paula Olaizola, Ibone Labiano, Aitor Esparza-Baquer, Marco Marzioni, Jose J G Marin, Luis Bujanda, Jesus M Banales
• Journal: Nature reviews. Gastroenterology & hepatology (Nat Rev Gastroenterol Hepatol) Vol. 16 Issue 2 Pg. 121-136 (02 2019) ISSN: 1759-5053 [Electronic] England
• PMID: 30451972 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Topics

• Animals
• Humans
• Liver (growth & development, metabolism)
• Liver Diseases (metabolism)
• Wnt Signaling Pathway