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

Autor:	Walko G; 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., Woodhouse S; 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., Pisco AO; 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., Rognoni E; 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., Liakath-Ali K; 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., Lichtenberger BM; 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., Mishra A; 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., Telerman SB; 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., Viswanathan P; 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., Logtenberg M; 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., Renz LM; 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., Donati G; 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., Quist SR; Clinic for Dermatology and Venerology, Otto-von-Guericke-University, Leipziger Straße 44, Magdeburg D-39120, Germany., Watt FM; 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.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2017 Mar 23; Vol. 8, pp. 14744. Date of Electronic Publication: 2017 Mar 23.
DOI:	10.1038/ncomms14744
Abstrakt:	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.
Databáze:	MEDLINE
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