Imperial College London
Alternate

DrGraemeBirdsey

Faculty of Medicine, National Heart & Lung Institute

Senior Lecturer in Vascular Science
 
 
 
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Contact

 

+44 (0)20 7594 8633g.birdsey Website

 
 
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Location

 

535ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Kostourou:2013:10.1038/ncomms3020,
author = {Kostourou, V and Lechertier, T and Reynolds, LE and Lees, DM and Baker, M and Jones, DT and Tavora, B and Ramjaun, AR and Birdsey, GM and Robinson, SD and Parsons, M and Randi, AM and Hart, IR and Hodivala-Dilke, K},
doi = {10.1038/ncomms3020},
journal = {Nature Communications},
title = {FAK-heterozygous mice display enhanced tumour angiogenesis},
url = {http://dx.doi.org/10.1038/ncomms3020},
volume = {4},
year = {2013}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Genetic ablation of endothelial focal adhesion kinase (FAK) can inhibit pathological angiogenesis, suggesting that loss of endothelial FAK is sufficient to reduce neovascularization. Here we show that reduced stromal FAK expression in FAK-heterozygous mice unexpectedly enhances both B16F0 and CMT19T tumour growth and angiogenesis. We further demonstrate that cell proliferation and microvessel sprouting, but not migration, are increased in serum-stimulated FAK-heterozygous endothelial cells. FAK-heterozygous endothelial cells display an imbalance in FAK phosphorylation at pY397 and pY861 without changes in Pyk2 or Erk1/2 activity. By contrast, serum-stimulated phosphorylation of Akt is enhanced in FAK-heterozygous endothelial cells and these cells are more sensitive to Akt inhibition. Additionally, low doses of a pharmacological FAK inhibitor, although too low to affect FAK autophosphorylation in vitro, can enhance angiogenesis ex vivo and tumour growth in vivo. Our results highlight a potential novel role for FAK as a nonlinear, dose-dependent regulator of angiogenesis where heterozygous levels of FAK enhance angiogenesis.
AU  - Kostourou,V
AU  - Lechertier,T
AU  - Reynolds,LE
AU  - Lees,DM
AU  - Baker,M
AU  - Jones,DT
AU  - Tavora,B
AU  - Ramjaun,AR
AU  - Birdsey,GM
AU  - Robinson,SD
AU  - Parsons,M
AU  - Randi,AM
AU  - Hart,IR
AU  - Hodivala-Dilke,K
DO  - 10.1038/ncomms3020
PY  - 2013///
SN  - 2041-1723
TI  - FAK-heterozygous mice display enhanced tumour angiogenesis
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/ncomms3020
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000323625700004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/73781
VL  - 4
ER  -
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