Author
Listed:
- Vassiliki Kostourou
(Vascular Adhesion Laboratory, BSRC Alexander Fleming, 34 Fleming Street, Vari
Centre for Tumour Biology, Barts Cancer Institute—a CR-UK Centre of Excellence, John Vane Science Centre, Queen Mary University of London, Charterhouse Square)
- Tanguy Lechertier
(Centre for Tumour Biology, Barts Cancer Institute—a CR-UK Centre of Excellence, John Vane Science Centre, Queen Mary University of London, Charterhouse Square)
- Louise E. Reynolds
(Centre for Tumour Biology, Barts Cancer Institute—a CR-UK Centre of Excellence, John Vane Science Centre, Queen Mary University of London, Charterhouse Square)
- Delphine M. Lees
(Centre for Tumour Biology, Barts Cancer Institute—a CR-UK Centre of Excellence, John Vane Science Centre, Queen Mary University of London, Charterhouse Square)
- Marianne Baker
(Centre for Tumour Biology, Barts Cancer Institute—a CR-UK Centre of Excellence, John Vane Science Centre, Queen Mary University of London, Charterhouse Square)
- Dylan T. Jones
(Centre for Tumour Biology, Barts Cancer Institute—a CR-UK Centre of Excellence, John Vane Science Centre, Queen Mary University of London, Charterhouse Square)
- Bernardo Tavora
(Centre for Tumour Biology, Barts Cancer Institute—a CR-UK Centre of Excellence, John Vane Science Centre, Queen Mary University of London, Charterhouse Square)
- Antoine R. Ramjaun
(Centre for Tumour Biology, Barts Cancer Institute—a CR-UK Centre of Excellence, John Vane Science Centre, Queen Mary University of London, Charterhouse Square)
- Graeme M. Birdsey
(Faculty of Medicine, Imperial College London, NHLI Cardiovascular Sciences, Hammersmith Hospital, Du Cane Road)
- Stephen D. Robinson
(Centre for Tumour Biology, Barts Cancer Institute—a CR-UK Centre of Excellence, John Vane Science Centre, Queen Mary University of London, Charterhouse Square
Present address: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR1 1RH, UK)
- Maddy Parsons
(New Hunts House, Kings College London)
- Anna M. Randi
(Faculty of Medicine, Imperial College London, NHLI Cardiovascular Sciences, Hammersmith Hospital, Du Cane Road)
- Ian R. Hart
(Centre for Tumour Biology, Barts Cancer Institute—a CR-UK Centre of Excellence, John Vane Science Centre, Queen Mary University of London, Charterhouse Square)
- Kairbaan Hodivala-Dilke
(Centre for Tumour Biology, Barts Cancer Institute—a CR-UK Centre of Excellence, John Vane Science Centre, Queen Mary University of London, Charterhouse Square)
Abstract
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.
Suggested Citation
Vassiliki Kostourou & Tanguy Lechertier & Louise E. Reynolds & Delphine M. Lees & Marianne Baker & Dylan T. Jones & Bernardo Tavora & Antoine R. Ramjaun & Graeme M. Birdsey & Stephen D. Robinson & Mad, 2013.
"FAK-heterozygous mice display enhanced tumour angiogenesis,"
Nature Communications, Nature, vol. 4(1), pages 1-11, October.
Handle:
RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3020
DOI: 10.1038/ncomms3020
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