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Integrin signalling regulates YAP and TAZ to control skin homeostasis

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Item Type:Article
Title:Integrin signalling regulates YAP and TAZ to control skin homeostasis
Creators Name:Elbediwy, A. and Vincent-Mistiaen, Z.I. and Spencer-Dene, B. and Stone, R.K. and Boeing, S. and Wculek, S.K. and Cordero, J. and Tan, E.H. and Ridgway, R. and Brunton, V.G. and Sahai, E. and Gerhardt, H. and Behrens, A. and Malanchi, I. and Sansom, O.J. and Thompson, B.J.
Abstract:The skin is a squamous epithelium that is continuously renewed by a population of basal layer stem/progenitor cells and can heal wounds. Here, we show that the transcription regulators YAP and TAZ localise to the nucleus in the basal layer of skin and are elevated upon wound healing. Skin-specific deletion of both YAP and TAZ in adult mice slows proliferation of basal layer cells, leads to hair loss and impairs regeneration after wounding. Contact with the basal extracellular matrix and consequent integrin-Src signalling is a key determinant of the nuclear localisation of YAP/TAZ in basal layer cells and in skin tumours. Contact with the basement membrane is lost in differentiating daughter cells, where YAP and TAZ become mostly cytoplasmic. In other types of squamous epithelia and squamous cell carcinomas, a similar control mechanism is present. By contrast, columnar epithelia differentiate an apical domain that recruits CRB3, Merlin (also known as NF2), KIBRA (also known as WWC1) and SAV1 to induce Hippo signalling and retain YAP/TAZ in the cytoplasm despite contact with the basal layer extracellular matrix. When columnar epithelial tumours lose their apical domain and become invasive, YAP/TAZ becomes nuclear and tumour growth becomes sensitive to the Src inhibitor Dasatinib.
Keywords:Hippo Pathway, Integrin, Yes-Associated Protein, TAZ, Stratified Squamous Epithelium, Animals, Mice
Publisher:Company of Biologists
Page Range:1674-1687
Date:15 May 2016
Official Publication:https://doi.org/10.1242/dev.133728
PubMed:View item in PubMed

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