期刊
NATURE COMMUNICATIONS
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms14744
关键词
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资金
- Wellcome Trust
- Wellcome Trust and Medical Research Council
- Department of Health via the National Institute for Health Research
- EU Marie Curie Intra-European Fellowship European Molecular Biology Organization (EMBO) [FP7-PEOPLE-2012-IEF326619]
- Federation of European Biochemical Societies (FEBS) [ALTF594-2014]
- BBSRC [BB/M007219/1] Funding Source: UKRI
- MRC [G1100073] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/M007219/1] Funding Source: researchfish
- Medical Research Council [G1100073] Funding Source: researchfish
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.
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