YAP and TAZ in epithelial stem cells: A sensor for cell polarity, mechanical forces and tissue damage. (13th May 2016)

• Record Type: Journal Article
• Authors: Elbediwy, Ahmed; Vincent‐Mistiaen, Zoé I.; Thompson, Barry J.
• Is Part Of: BioEssays. Volume 38:Number 7(2016:Jul.)
• Page Start: 644
• Page End: 653
• Publication Date: 2016-05-13
• Subjects: epithelial polarity -- Hippo pathway -- mechanosensing -- mechanotransduction -- TAZ -- wound healing -- YAP; Molecular biology -- Periodicals; Cytology -- Periodicals; Developmental biology -- Periodicals; 572.8
• DOI: 10.1002/bies.201600037
• Languages: English
• ISSNs: 0265-9247

Abstract

Abstract : 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. Abstract : 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.