The Hippo pathway in intestinal regeneration and disease

Nat Rev Gastroenterol Hepatol. 2016 Jun;13(6):324-37. doi: 10.1038/nrgastro.2016.59. Epub 2016 May 5.

Abstract

The Hippo pathway is a signalling cascade conserved from Drosophila melanogaster to mammals. The mammalian core kinase components comprise MST1 and MST2, SAV1, LATS1 and LATS2 and MOB1A and MOB1B. The transcriptional co-activators YAP1 and TAZ are the downstream effectors of the Hippo pathway and regulate target gene expression. Hippo signalling has crucial roles in the control of organ size, tissue homeostasis and regeneration, and dysregulation of the Hippo pathway can lead to uncontrolled cell growth and malignant transformation. Mammalian intestine consists of a stem cell compartment as well as differentiated cells, and its ability to regenerate rapidly after injury makes it an excellent model system to study tissue homeostasis, regeneration and tumorigenesis. Several studies have established the important role of the Hippo pathway in these processes. In addition, crosstalk between Hippo and other signalling pathways provides tight, yet versatile, regulation of tissue homeostasis. In this Review, we summarize studies on the role of the Hippo pathway in the intestine on these physiological processes and the underlying mechanisms responsible, and discuss future research directions and potential therapeutic strategies targeting Hippo signalling in intestinal disease.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Bone Morphogenetic Proteins / metabolism
  • Carcinogenesis / metabolism
  • Cell Adhesion / physiology
  • Colonic Neoplasms / physiopathology
  • Drosophila melanogaster
  • Hedgehog Proteins / metabolism
  • Homeostasis / physiology
  • Humans
  • Intestine, Large / physiology*
  • Intestine, Small / physiology*
  • Irritable Bowel Syndrome / physiopathology
  • Liver Neoplasms / physiopathology
  • Mammals
  • Organ Size
  • Phosphoproteins / metabolism
  • Protein-Serine-Threonine Kinases / metabolism*
  • Receptors, G-Protein-Coupled / physiology
  • Receptors, Notch / metabolism
  • Regeneration / physiology*
  • Signal Transduction / physiology*
  • Stress, Physiological / physiology
  • Transcription Factors / metabolism
  • Wnt Signaling Pathway / physiology

Substances

  • Adaptor Proteins, Signal Transducing
  • Bone Morphogenetic Proteins
  • Hedgehog Proteins
  • Phosphoproteins
  • Receptors, G-Protein-Coupled
  • Receptors, Notch
  • TAZ protein, human
  • Transcription Factors
  • YAP1 (Yes-associated) protein, human
  • Hippo protein, human
  • Protein-Serine-Threonine Kinases