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Nat Commun. 2017 Mar 23;8:14744. doi: 10.1038/ncomms14744.

A genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells.

Author information

1
Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences &Medicine, King's College London, 28th Floor, Tower Wing, Guy's Hospital, London SE1 9RT, UK.
2
Clinic for Dermatology and Venerology, Otto-von-Guericke-University, Leipziger Straße 44, Magdeburg D-39120, Germany.

Abstract

Individual human epidermal cells differ in their self-renewal ability. To uncover the molecular basis for this heterogeneity, we performed genome-wide pooled RNA interference screens and identified genes conferring a clonal growth advantage on normal and neoplastic (cutaneous squamous cell carcinoma, cSCC) human epidermal cells. The Hippo effector YAP was amongst the top positive growth regulators in both screens. By integrating the Hippo network interactome with our data sets, we identify WW-binding protein 2 (WBP2) as an important co-factor of YAP that enhances YAP/TEAD-mediated gene transcription. YAP and WPB2 are upregulated in actively proliferating cells of mouse and human epidermis and cSCC, and downregulated during terminal differentiation. WBP2 deletion in mouse skin results in reduced proliferation in neonatal and wounded adult epidermis. In reconstituted epidermis YAP/WBP2 activity is controlled by intercellular adhesion rather than canonical Hippo signalling. We propose that defective intercellular adhesion contributes to uncontrolled cSCC growth by preventing inhibition of YAP/WBP2.

PMID:
28332498
PMCID:
PMC5376649
DOI:
10.1038/ncomms14744
[Indexed for MEDLINE]
Free PMC Article

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