Role of the Hippo Pathway in Fibrosis and Cancer

Cells. 2019 May 16;8(5):468. doi: 10.3390/cells8050468.

Abstract

The Hippo pathway is the key player in various signaling processes, including organ development and maintenance of tissue homeostasis. This pathway comprises a core kinases module and transcriptional activation module, representing a highly conserved mechanism from Drosophila to vertebrates. The central MST1/2-LATS1/2 kinase cascade in this pathway negatively regulates YAP/TAZ transcription co-activators in a phosphorylation-dependent manner. Nuclear YAP/TAZ bind to transcription factors to stimulate gene expression, contributing to the regenerative potential and regulation of cell growth and death. Recent studies have also highlighted the potential role of Hippo pathway dysfunctions in the pathology of several diseases. Here, we review the functional characteristics of the Hippo pathway in organ fibrosis and tumorigenesis, and discuss its potential as new therapeutic targets.

Keywords: ECM; EMT; LATS1/2; MST1/2; TAZ; YAP; cancer; fibrosis; myofibroblast.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Epigenesis, Genetic
  • Epithelial-Mesenchymal Transition
  • Fibrosis / metabolism
  • Humans
  • Mice
  • Neoplasms / metabolism*
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism
  • Trans-Activators
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • Tumor Microenvironment
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • WWTR1 protein, human
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Protein Serine-Threonine Kinases