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

  • Nat Rev Gastroenterol Hepatol. 2019 Feb;16(2):121-136. doi: 10.1038/s41575-018-0075-9.
Maria J Perugorria  1  2  3 ,  Paula Olaizola  1 ,  Ibone Labiano  1 ,  Aitor Esparza-Baquer  1 ,  Marco Marzioni  4 ,  Jose J G Marin  2  5 ,  Luis Bujanda  1  2 ,  Jesus M Banales  6  7  8
Affiliations
  • 1. Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital - University of the Basque Country (UPV/EHU), San Sebastian, Spain.
  • 2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Institute of Health (ISCIII), Madrid, Spain.
  • 3. Ikerbasque, Basque Foundation for Science, Bilbao, Spain.
  • 4. Department of Gastroenterology, Università Politecnica delle Marche, Ancona, Italy.
  • 5. Experimental Hepatology and Drug Targeting (HEVEFARM), Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain.
  • 6. Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital - University of the Basque Country (UPV/EHU), San Sebastian, Spain. [email protected].
  • 7. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Institute of Health (ISCIII), Madrid, Spain. [email protected].
  • 8. Ikerbasque, Basque Foundation for Science, Bilbao, Spain. [email protected].
PMID: 30451972 DOI: 10.1038/s41575-018-0075-9
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.