Li, XiujuanPadhan, NarendraSjöström, Elisabet O.Roche, Francis P.Testini, ChiaraHonkura, NaokiSáinz-Jaspeado, MiguelGordon, EmmaBentley, KatiePhilippides, AndrewTolmachev, VladimirDejana, ElisabettaStan, Radu V.Vestweber, DietmarBallmer-Hofer, KurtBetsholtz, ChristerPietras, KristianJansson, LeifClaesson-Welsh, Lena2016-11-182016Li, X., N. Padhan, E. O. Sjöström, F. P. Roche, C. Testini, N. Honkura, M. Sáinz-Jaspeado, et al. 2016. “VEGFR2 pY949 signalling regulates adherens junction integrity and metastatic spread.” Nature Communications 7 (1): 11017. doi:10.1038/ncomms11017. http://dx.doi.org/10.1038/ncomms11017.2041-1723http://nrs.harvard.edu/urn-3:HUL.InstRepos:29407766The specific role of VEGFA-induced permeability and vascular leakage in physiology and pathology has remained unclear. Here we show that VEGFA-induced vascular leakage depends on signalling initiated via the VEGFR2 phosphosite Y949, regulating dynamic c-Src and VE-cadherin phosphorylation. Abolished Y949 signalling in the mouse mutant Vegfr2Y949F/Y949F leads to VEGFA-resistant endothelial adherens junctions and a block in molecular extravasation. Vessels in Vegfr2Y949F/Y949F mice remain sensitive to inflammatory cytokines, and vascular morphology, blood pressure and flow parameters are normal. Tumour-bearing Vegfr2Y949F/Y949F mice display reduced vascular leakage and oedema, improved response to chemotherapy and, importantly, reduced metastatic spread. The inflammatory infiltration in the tumour micro-environment is unaffected. Blocking VEGFA-induced disassembly of endothelial junctions, thereby suppressing tumour oedema and metastatic spread, may be preferable to full vascular suppression in the treatment of certain cancer forms.en-USJournal Article2016-11-1810.1038/ncomms11017