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

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

Author information

1
The Stem Cell Program, Department of Medicine, Boston Children's Hospital, Boston, MA 02115, United States; Division of Gastroenterology and Nutrition, Department of Medicine, Boston Children's Hospital, Boston, MA 02115, United States. Electronic address: dean.yimlamai@childrens.harvard.edu.
2
The Stem Cell Program, Department of Medicine, Boston Children's Hospital, Boston, MA 02115, United States; Division of Gastroenterology and Nutrition, Department of Medicine, Boston Children's Hospital, Boston, MA 02115, United States.
3
The Stem Cell Program, Department of Medicine, Boston Children's Hospital, Boston, MA 02115, United States; Harvard Stem Cell Institute, Cambridge, MA 02138, United States; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, United States. Electronic address: fernando.camargo@childrens.harvard.edu.

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

PMID:
26226451
PMCID:
PMC4654680
DOI:
10.1016/j.jhep.2015.07.008
[Indexed for MEDLINE]
Free PMC Article

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