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DLC1 is a direct target of activated YAP/TAZ that drives collective migration and sprouting angiogenesis

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Item Type:Article
Title:DLC1 is a direct target of activated YAP/TAZ that drives collective migration and sprouting angiogenesis
Creators Name:van der Stoel, M. and Schimmel, L. and Nawaz, K. and van Stalborch, A.M. and de Haan, A. and Klaus-Bergmann, A. and Valent, E.T. and Koenis, D.S. and van Nieuw Amerongen, G.P. and de Vries, C.J. and de Waard, V. and Gloerich, M. and van Buul, J.D. and Huveneers, S.
Abstract:Endothelial YAP/TAZ signaling is crucial for sprouting angiogenesis and vascular homeostasis. Yet the underlying molecular mechanisms that explain how YAP/TAZ control the vasculature remain unclear. This study reveals that the focal adhesion protein Deleted-in-Liver-Cancer 1 (DLC1) is a direct transcriptional target of the activated YAP/TAZ-TEAD complex. We find that substrate stiffening and VEGF stimuli promote expression of DLC1 in endothelial cells. In turn, DLC1 expression levels are YAP- and TAZ-dependent, and constitutive activation of YAP is sufficient to drive DLC1 expression. DLC1 is needed to limit F-actin fiber formation, integrin-based focal adhesion lifetime and integrin-mediated traction forces. Depletion of endothelial DLC1 strongly perturbs cell polarization in directed collective migration and inhibits the formation of angiogenic sprouts. Importantly, ectopic expression of DLC1 is sufficient to restore migration and angiogenic sprouting in YAP-depleted cells. Together, these findings point towards a crucial and prominent role for DLC1 in YAP/TAZ-driven endothelial adhesion remodeling and collective migration during angiogenesis.
Keywords:Mechanotransduction, Endothelium, Adhesion, Integrin, YAP, Angiogenesis
Source:Journal of Cell Science
ISSN:0021-9533
Publisher:Company of Biologists
Volume:133
Number:3
Page Range:jcs239947
Date:12 February 2020
Additional Information:Copyright © 2020. Published by The Company of Biologists Ltd.
Official Publication:https://doi.org/10.1242/jcs.239947
PubMed:View item in PubMed

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