VEGFR2 pY949 signalling regulates adherens junction integrity and metastatic spread
Författare
Summary, in English
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.
Avdelning/ar
- Experimentell onkologi
- Avdelningen för translationell cancerforskning
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publiceringsår
2016-03-23
Språk
Engelska
Publikation/Tidskrift/Serie
Nature Communications
Volym
7
Dokumenttyp
Artikel i tidskrift
Förlag
Nature Publishing Group
Ämne
- Cell and Molecular Biology
Status
Published
Forskningsgrupp
- Experimental oncology
ISBN/ISSN/Övrigt
- ISSN: 2041-1723