The formation of blood vessels involves the collective movement, growth and differentiation of endothelial cells. Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) activity, which is modulated by extracellular matrix stiffness, is known to regulate developmental angiogenesis. However, the downstream transcriptional targets of YAP/TAZ signalling have so far remained elusive. Now, Stephan Huveneers and colleagues (van der Stoel et al., 2020) find that the focal adhesion protein deleted-in-liver-cancer 1 (DLC1) is a direct target of active YAP/TAZ. The authors first show in primary human umbilical vein endothelial cells that extracellular matrix stiffness controls DLC1 expression both at the transcript and protein level. A constitutively active variant of YAP revealed that, even on soft substrates, YAP is sufficient to drive DLC1 expression. The authors then focus on identifying the cellular processes regulated by DLC1. Combining shRNA knockdown approaches and imaging, they find that DLC1 is needed for integrin-based focal adhesion disassembly, cell polarization, collective cell migration and sprouting angiogenesis. Finally, DLC1 overexpression was sufficient to restore the migration and sprouting defects caused by YAP depletion. Overall, these results establish a key role for DLC1 in YAP/TAZ-driven collective migration and sprouting angiogenesis.
