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

Autor:	van der Stoel M; Amsterdam UMC, University of Amsterdam, location AMC, Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences, 1105 AZ Amsterdam, The Netherlands., Schimmel L; Sanquin Research and Landsteiner Laboratory, Department of Molecular and Cellular Hemostasis, University of Amsterdam, 1066 CX Amsterdam, The Netherlands., Nawaz K; Sanquin Research and Landsteiner Laboratory, Department of Molecular and Cellular Hemostasis, University of Amsterdam, 1066 CX Amsterdam, The Netherlands., van Stalborch AM; Sanquin Research and Landsteiner Laboratory, Department of Molecular and Cellular Hemostasis, University of Amsterdam, 1066 CX Amsterdam, The Netherlands., de Haan A; Amsterdam UMC, University of Amsterdam, location AMC, Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences, 1105 AZ Amsterdam, The Netherlands., Klaus-Bergmann A; Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.; DZHK (German Center for Cardiovascular Research), 10785 Berlin, Germany., Valent ET; Amsterdam UMC, Free University, location VUMC, Department of Physiology, Amsterdam Cardiovascular Sciences, 1081 HV Amsterdam, The Netherlands., Koenis DS; Amsterdam UMC, University of Amsterdam, location AMC, Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences, 1105 AZ Amsterdam, The Netherlands., van Nieuw Amerongen GP; Amsterdam UMC, Free University, location VUMC, Department of Physiology, Amsterdam Cardiovascular Sciences, 1081 HV Amsterdam, The Netherlands., de Vries CJ; Amsterdam UMC, University of Amsterdam, location AMC, Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences, 1105 AZ Amsterdam, The Netherlands., de Waard V; Amsterdam UMC, University of Amsterdam, location AMC, Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences, 1105 AZ Amsterdam, The Netherlands., Gloerich M; University Medical Center Utrecht, Center for Molecular Medicine, Dept. Molecular Cancer Research, 3584 CX Utrecht, The Netherlands., van Buul JD; Sanquin Research and Landsteiner Laboratory, Department of Molecular and Cellular Hemostasis, University of Amsterdam, 1066 CX Amsterdam, The Netherlands.; Leeuwenhoek Centre for Advanced Microscopy (LCAM), section Molecular Cytology at Swammerdam Institute for Life Sciences (SILS) at University of Amsterdam, 1098 XH Amsterdam, The Netherlands., Huveneers S; Amsterdam UMC, University of Amsterdam, location AMC, Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences, 1105 AZ Amsterdam, The Netherlands s.huveneers@amsterdamumc.nl.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2020 Feb 12; Vol. 133 (3). Date of Electronic Publication: 2020 Feb 12.
DOI:	10.1242/jcs.239947
Abstrakt:	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. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2020. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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