Disease implications of the Hippo/YAP pathway

Trends Mol Med. 2015 Apr;21(4):212-22. doi: 10.1016/j.molmed.2015.01.003. Epub 2015 Feb 18.

Abstract

The Hippo signaling pathway is important for controlling organ size and tissue homeostasis. Originally identified in Drosophila melanogaster, the core components of the Hippo pathway are highly conserved in mammals. The Hippo pathway can be modulated by a wide range of stimuli, including G protein-coupled receptor (GPCR) signaling, changes in the actin cytoskeleton, cell-cell contact, and cell polarity. When activated, the Hippo pathway functions as a tumor suppressor to limit cell growth. However, dysregulation by genetic inactivation of core pathway components or amplification or gene fusion of its downstream effectors results in increased cell proliferation and decreased apoptosis and differentiation. Unsurprisingly, this can lead to tissue overgrowth, tumorigenesis, and many other diseases.

Keywords: Hippo; TAZ; YAP; cancer; disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Carcinogenesis
  • Cell Proliferation
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Neoplastic
  • Hippo Signaling Pathway
  • Homeostasis
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mammals
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Organ Size
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • YAP-Signaling Proteins

Substances

  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Receptors, G-Protein-Coupled
  • Trans-Activators
  • Transcription Factors
  • YAP-Signaling Proteins
  • Yki protein, Drosophila
  • Protein Serine-Threonine Kinases
  • hpo protein, Drosophila