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J Hepatol. 2014 Apr;60(4):885-90. doi: 10.1016/j.jhep.2013.11.028. Epub 2013 Dec 3.

Notch signaling and new therapeutic options in liver disease.

Author information

1
Department of Surgery and Interdisciplinary Medicine, University of Milano-Bicocca, Milan, Italy.
2
Department of Surgery and Interdisciplinary Medicine, University of Milano-Bicocca, Milan, Italy; Liver Center & Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA. Electronic address: mario.strazzabosco@yale.edu.

Abstract

Notch signaling is a crucial determinant of cell fate decision during development and disease in several organs. Notch effects are strictly dependent on the cellular context in which it is activated. In the liver, Notch signaling is involved in biliary tree development and tubulogenesis. Recent advances have shed light on Notch as a critical player in liver regeneration and repair, as well as in liver metabolism and inflammation and cancer. Notch signaling is finely regulated at several levels. The complexity of the pathway provides several possible targets for development of therapeutic agents able to inhibit Notch. Recent reports have shown that persistent activation of Notch signaling is associated with liver malignancies, particularly hepatocellular with stem cell features and cholangiocarcinoma. These novel findings suggest that interfering with the aberrant activation of the Notch pathway may have therapeutic relevance. However, further studies are needed to clarify the mechanisms regulating physiologic and pathologic Notch activation in the adult liver, to better understand the mechanistic role(s) of Notch in liver diseases and to develop safe and specific therapeutic agents.

KEYWORDS:

Liver cancer; Liver repair; Notch inhibitors; Notch signaling

PMID:
24308992
DOI:
10.1016/j.jhep.2013.11.028
[Indexed for MEDLINE]
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