Emerging evidence on the role of the Hippo/YAP pathway in liver physiology and cancer

J Hepatol. 2015 Dec;63(6):1491-501. doi: 10.1016/j.jhep.2015.07.008. Epub 2015 Jul 28.

Abstract

The Hippo pathway and its regulatory target, YAP, has recently emerged as an important biochemical signaling pathway that tightly governs epithelial tissue growth. Initially defined in Drosophilia, this pathway has shown remarkable conservation in vertebrate systems with many components of the Hippo/YAP pathway showing biochemical and functional conservation. The liver is particularly sensitive to changes in Hippo/YAP signaling with rapid increases in liver size becoming manifest on the order of days to weeks after perturbation. The first identified direct targets of Hippo/YAP signaling were pro-proliferative and anti-apoptotic gene programs, but recent work has now implicated this pathway in cell fate choice, stem cell maintenance/renewal, epithelial to mesenchymal transition, and oncogenesis. The mechanisms by which Hippo/YAP signaling is changed endogenously are beginning to come to light as well as how this pathway interacts with other signaling pathways, and important details for designing new therapeutic interventions. This review focuses on the known roles for Hippo/YAP signaling in the liver and promising avenues for future study.

Keywords: Hippo signaling; Liver regeneration; Stem cell biology.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Drosophila Proteins / physiology
  • Humans
  • Intracellular Signaling Peptides and Proteins / physiology
  • Liver / physiology*
  • Liver Neoplasms / physiopathology*
  • Liver Regeneration / physiology
  • Models, Biological
  • Nuclear Proteins / physiology
  • Organ Size / physiology
  • Protein-Serine-Threonine Kinases / physiology
  • Signal Transduction / physiology
  • Trans-Activators / physiology

Substances

  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Trans-Activators
  • Yki protein, Drosophila
  • Protein-Serine-Threonine Kinases
  • hpo protein, Drosophila