FAK-heterozygous mice display enhanced tumour angiogenesis

Kostourou, Vassiliki, Lechertier, Tanguy, Reynolds, Louise E., Lees, Delphine M., Baker, Marianne, Jones, Dylan T., Tavora, Bernardo, Ramjuan, Antoine R., Birdsey, Graeme M., Robinson, Stephen R. ORCID: https://orcid.org/0000-0002-6606-7588, Parsons, Maddy, Randi, Anna M., Hart, Ian R. and Hodivala-Dilke, Kairbaan (2013) FAK-heterozygous mice display enhanced tumour angiogenesis. Nature Communications, 4. ISSN 2041-1723

Full text not available from this repository. (Request a copy)


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.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
UEA Research Groups: Faculty of Science > Research Groups > Cells and Tissues
Depositing User: Pure Connector
Date Deposited: 25 Jun 2013 10:55
Last Modified: 23 Apr 2023 00:03
URI: https://ueaeprints.uea.ac.uk/id/eprint/42778
DOI: 10.1038/ncomms3020

Actions (login required)

View Item View Item