Hippo pathway regulation of gastrointestinal tissues

Annu Rev Physiol. 2015:77:201-27. doi: 10.1146/annurev-physiol-021014-071733. Epub 2014 Sep 29.

Abstract

The Hippo pathway plays a crucial role in regulating tissue homeostasis and organ size, and its deregulation is frequently observed in human cancer. Yap is the major effector of and is inhibited by the Hippo pathway. In mouse model studies, inducible Yap expression in multiple tissues results in organ overgrowth. In the liver, knockout of upstream Hippo pathway components or transgenic expression of Yap leads to liver enlargement and hepatocellular carcinoma. In the small intestine or colon, deletion of upstream Hippo pathway components also results in expansion of intestinal progenitor cells and eventual development of adenomas. Genetic deletion of Yap in the intestine does not change the intestinal structure, but Yap is essential for intestinal repair upon certain types of tissue injury. The function of the Hippo pathway has also been studied in other gastrointestinal tissues, including the pancreas and stomach. Here we provide a brief overview of the Hippo pathway and discuss the physiological and pathological functions of this tumor suppressor pathway in gastrointestinal tissues.

Keywords: Mst1; Mst2; Yap; cancer; intestine; liver; regeneration.

Publication types

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

MeSH terms

  • Acyltransferases
  • Adaptor Proteins, Signal Transducing / physiology
  • Animals
  • Cell Cycle Proteins
  • Disease Models, Animal
  • Gastrointestinal Neoplasms / physiopathology
  • Gastrointestinal Tract / physiology*
  • Hippo Signaling Pathway
  • Homeostasis / physiology*
  • Humans
  • Mice
  • Phosphoproteins / physiology
  • Protein Serine-Threonine Kinases / physiology*
  • Regeneration / physiology*
  • Signal Transduction / physiology*
  • Transcription Factors / physiology
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Phosphoproteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Yap1 protein, mouse
  • Acyltransferases
  • tafazzin protein, mouse
  • TAFAZZIN protein, human
  • Protein Serine-Threonine Kinases