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YAP and TAZ in epithelial stem cells: A sensor for cell polarity, mechanical forces and tissue damage

Ahmed Elbediwy1, Zoé I Vincent-Mistiaen1, Barry J Thompson1

  • 1Epithelial Biology Laboratory, Francis Crick Institute, London, UK.

Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology
|May 14, 2016
PubMed

Insights

YAP/TAZ activity is regulated by cell polarity, with apical signaling inhibiting it and basal signaling activating it. This polarity sensing controls cell proliferation in tissues and cancers.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • YAP/TAZ are transcriptional co-activators crucial for cell proliferation in epithelial tissues and cancers.
  • The precise physiological regulation of YAP/TAZ activity remains incompletely understood.

Purpose of the Study:

  • To review recent findings on the physiological regulation of YAP/TAZ.
  • To elucidate YAP/TAZ's role as sensors of epithelial cell polarity.

Main Methods:

  • Literature review of recent reports on YAP/TAZ regulation.
  • Analysis of signaling pathways (Crumbs/CRB-Hippo/MST-Warts/LATS and Integrins/Src) involved in YAP/TAZ activation and inhibition.

Main Results:

  • YAP/TAZ act as polarity sensors: inhibited by apical membrane domain differentiation, activated by basal membrane domain contact with the extracellular matrix.
  • Apical signaling involves the Crumbs/CRB-Hippo/MST-Warts/LATS cascade, leading to YAP/TAZ phosphorylation and inhibition.
  • Basal signaling involves Integrins and Src family kinases, leading to YAP/TAZ phosphorylation and activation, influencing localization in stem/differentiated cells.

Conclusions:

  • YAP/TAZ activity is tightly controlled by epithelial cell polarity.
  • Mechanical forces, tissue damage, and receptor tyrosine kinases can further modulate YAP/TAZ activity via kinase pathways.
Keywords:
Hippo pathwayTAZYAPepithelial polaritymechanosensingmechanotransductionwound healing

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