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Kristian Pietras

Kristian Pietras

Research team manager

Kristian Pietras

VEGFR2 pY949 signalling regulates adherens junction integrity and metastatic spread

Author

  • Xiujuan Li
  • Narendra Padhan
  • Elisabet O Sjöström
  • Francis P Roche
  • Chiara Testini
  • Naoki Honkura
  • Miguel Sáinz-Jaspeado
  • Emma Gordon
  • Katie Bentley
  • Andrew Philippides
  • Vladimir Tolmachev
  • Elisabetta Dejana
  • Radu V Stan
  • Dietmar Vestweber
  • Kurt Ballmer-Hofer
  • Christer Betsholtz
  • Kristian Pietras
  • Leif Jansson
  • Lena Claesson-Welsh
Show all

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.

Department/s

  • Experimental oncology
  • Division of Translational Cancer Research
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year

2016-03-23

Language

English

Publication/Series

Nature Communications

Volume

7

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Experimental oncology

ISBN/ISSN/Other

  • ISSN: 2041-1723