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

Gernot Walko, Samuel Woodhouse, Angela Oliveira Pisco, Emanuel Rognoni, Kifayathullah Liakath-Ali, Beate M. Lichtenberger, Ajay Mishra, Stephanie B. Telerman, Priyalakshmi Viswanathan, Meike Logtenberg, Lisa M. Renz, Giacomo Donati, Sven R. Quist and Fiona M. Watt ()
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Gernot Walko: Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences & Medicine, King’s College London
Samuel Woodhouse: Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences & Medicine, King’s College London
Angela Oliveira Pisco: Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences & Medicine, King’s College London
Emanuel Rognoni: Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences & Medicine, King’s College London
Kifayathullah Liakath-Ali: Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences & Medicine, King’s College London
Beate M. Lichtenberger: Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences & Medicine, King’s College London
Ajay Mishra: Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences & Medicine, King’s College London
Stephanie B. Telerman: Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences & Medicine, King’s College London
Priyalakshmi Viswanathan: Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences & Medicine, King’s College London
Meike Logtenberg: Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences & Medicine, King’s College London
Lisa M. Renz: Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences & Medicine, King’s College London
Giacomo Donati: Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences & Medicine, King’s College London
Sven R. Quist: Clinic for Dermatology and Venerology, Otto-von-Guericke-University
Fiona M. Watt: Centre for Stem Cells and Regenerative Medicine, Faculty of Life Sciences & Medicine, King’s College London

Nature Communications, 2017, vol. 8, issue 1, 1-16

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14744

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