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

Miesje van der Stoel, Lilian Schimmel, Kalim Nawaz, Anne-Marieke van Stalborch, Annett de Haan, Alexandra Klaus-Bergmann, Erik T. Valent, Duco S. Koenis, Geerten P. van Nieuw Amerongen, Carlie J. de Vries, Vivian de Waard, Martijn Gloerich (+2 others)
2020 Journal of Cell Science  
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-
more » ... n 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.
doi:10.1242/jcs.239947 pmid:31964713 fatcat:orisfxypovh7rgldya2u3vuqym