| First Author | Li X | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 11017 | PubMed ID | 27005951 |
| Mgi Jnum | J:236742 | Mgi Id | MGI:5807012 |
| Doi | 10.1038/ncomms11017 | Citation | Li X, et al. (2016) VEGFR2 pY949 signalling regulates adherens junction integrity and metastatic spread. Nat Commun 7:11017 |
| abstractText | The 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 Vegfr2(Y949F/Y949F) leads to VEGFA-resistant endothelial adherens junctions and a block in molecular extravasation. Vessels in Vegfr2(Y949F/Y949F) mice remain sensitive to inflammatory cytokines, and vascular morphology, blood pressure and flow parameters are normal. Tumour-bearing Vegfr2(Y949F/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. |
