Open AccessEndothelial FAK is required for tumour angiogenesis
Author(s) -
Tavora Bernardo,
Batista Silvia,
Reynolds Louise E.,
Jadeja Shalini,
Robinson Stephen,
Kostourou Vassiliki,
Hart Ian,
Fruttiger Marcus,
Parsons Maddy,
HodivalaDilke Kairbaan M.
Publication year - 2010
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201000106
Subject(s) - pdgfb , angiogenesis , focal adhesion , cancer research , neovascularization , vascular endothelial growth factor a , vascular endothelial growth factor , biology , endothelial stem cell , microbiology and biotechnology , growth factor , signal transduction , platelet derived growth factor receptor , in vitro , receptor , biochemistry , vegf receptors
Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that plays a fundamental role in integrin and growth factor mediated signalling and is an important player in cell migration and proliferation, processes vital for angiogenesis. However, the role of FAK in adult pathological angiogenesis is unknown. We have generated endothelial‐specific tamoxifen‐inducible FAK knockout mice by crossing FAK‐floxed (FAKfl/fl) mice with the platelet derived growth factor b ( Pdgfb )‐iCreER mice. Tamoxifen‐treatment of Pdgfb ‐iCreER;FAKfl/fl mice results in FAK deletion in adult endothelial cells (ECs) without any adverse effects. Importantly however, endothelial FAK‐deletion in adult mice inhibited tumour growth and reduced tumour angiogenesis. Furthermore, in in vivo angiogenic assays FAK deletion impairs vascular endothelial growth factor (VEGF)‐induced neovascularization. In addition, in vitro deletion of FAK in ECs resulted in reduced VEGF‐stimulated Akt phosphorylation and correlating reduced cellular proliferation as well as increased cell death. Our data suggest that FAK is required for adult pathological angiogenesis and validates FAK as a possible target for anti‐angiogenic therapies.