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

• Published in: BioEssays Vol. 38; no. 7; pp. 644 - 653
• Main Authors: Elbediwy, Ahmed, Vincent-Mistiaen, Zoé I., Thompson, Barry J.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.07.2016; Wiley Subscription Services, Inc; John Wiley and Sons Inc
• Subjects: Animals; Biomechanical Phenomena; Cell Cycle Proteins; Cell Polarity; Drosophila; Drosophila Proteins - physiology; epithelial polarity; Epithelium - metabolism; Epithelium - physiology; Hippo pathway; Humans; Kinases; mechanosensing; mechanotransduction; Nuclear Proteins - physiology; Phosphotransferases (Alcohol Group Acceptor) - physiology; Prospects & Overviews; Repressor Proteins; RNA-Binding Proteins; Signal Transduction; Stem Cells - metabolism; Stem Cells - physiology; TAZ; Trans-Activators - physiology; Transcription Factors - physiology; wound healing; YAP; epithelial polarity; mechanosensing; wound healing; Hippo pathway; mechanotransduction; YAP; TAZ
• ISSN: 0265-9247; 1521-1878
• DOI: 10.1002/bies.201600037

The YAP/TAZ family of transcriptional co‐activators drives cell proliferation in epithelial tissues and cancers. Yet, how YAP and TAZ are physiologically regulated remains unclear. Here we review recent reports that YAP and TAZ act primarily as sensors of epithelial cell polarity, being inhibited when cells differentiate an apical membrane domain, and being activated when cells contact the extracellular matrix via their basal membrane domain. Apical signalling occurs via the canonical Crumbs/CRB‐Hippo/MST‐Warts/LATS kinase cascade to phosphorylate and inhibit YAP/TAZ. Basal signalling occurs via Integrins and Src family kinases to phosphorylate and activate YAP/TAZ. Thus, YAP/TAZ is localised to the nucleus in basal stem/progenitor cells and cytoplasm in differentiated squamous cells or columnar cells. In addition, other signals such as mechanical forces, tissue damage and possibly receptor tyrosine kinases (RTKs) can influence MST‐LATS or Src family kinase activity to modulate YAP/TAZ activity. YAP and TAZ are sensors of cell polarity, being nuclear in stem cells and cytoplasmic in differentiated epithelial cells due to Hippo pathway signalling. In addition, YAP/TAZ (Yorkie in Drosophila) can respond to mechanical forces and tissue damage to drive stem cell proliferation responses.