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, Jaap D. van Buul, Stephan Huveneers

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Endothelial YAP/TAZ (YAP is also known as YAP1, and TAZ as WWTR1) signaling is crucial for sprouting angiogenesis and vascular homeostasis. However, 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.This article has an associated First Person interview with the first author of the paper.

Original languageEnglish
Article number jcs239947
JournalJournal of Cell Science
Volume133
Issue number3
DOIs
Publication statusPublished - 12 Feb 2020

Cite this

van der Stoel, M., Schimmel, L., Nawaz, K., van Stalborch, A. M., de Haan, A., Klaus-Bergmann, A., ... Huveneers, S. (2020). DLC1 is a direct target of activated YAP/TAZ that drives collective migration and sprouting angiogenesis. Journal of Cell Science, 133(3), [ jcs239947 ]. https://doi.org/10.1242/jcs.239947