Integrin signalling regulates YAP and TAZ to control skin homeostasis

Elbediwy, A. et al. (2016) Integrin signalling regulates YAP and TAZ to control skin homeostasis. Development, 143(10), pp. 1674-1687. (doi:10.1242/dev.133728) (PMID:26989177) (PMCID:PMC4874484)

Elbediwy, A. et al. (2016) Integrin signalling regulates YAP and TAZ to control skin homeostasis. Development, 143(10), pp. 1674-1687. (doi:10.1242/dev.133728) (PMID:26989177) (PMCID:PMC4874484)

[img]
Preview
Text
124262.pdf - Published Version
Available under License Creative Commons Attribution.

2MB

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tan, Dr Ee and Cordero, Dr Julia and Ridgway, Dr Rachel and Brunton, Dr Valerie and Sansom, Professor Owen
Authors: Elbediwy, A., Vincent-Mistiaen, Z. I., Spencer-Dene, B., Stone, R. K., Boeing, S., Wculek, S. K., Cordero, J., Tan, E. H., Ridgway, R., Brunton, V. G., Sahai, E., Gerhardt, H., Behrens, A., Malanchi, I., Sansom, O. J., and Thompson, B. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Development
Publisher:Company of Biologists
ISSN:0950-1991
ISSN (Online):1477-9129
Published Online:17 May 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Development 143(10):1674-1687
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record