FAK-heterozygous mice display enhanced tumour angiogenesis
| Autor: | Kairbaan Hodivala-Dilke, Marianne Baker, Louise E. Reynolds, Madeline Parsons, Dylan T. Jones, Ian R. Hart, Graeme M. Birdsey, Anna M. Randi, Delphine M. Lees, Bernardo Tavora, Antoine R. Ramjaun, Vassiliki Kostourou, Tanguy Lechertier, Stephen D. Robinson |
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| Přispěvatelé: | British Heart Foundation |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Talin
Angiogenesis General Physics and Astronomy Cell Separation Neovascularization Mice Subcutaneous Tissue Neoplasms TYROSINE-861 PHOSPHORYLATION Multidisciplinary biology Neovascularization Pathologic FOCAL-ADHESION KINASE Immunohistochemistry Cell biology Tumor Burden Multidisciplinary Sciences SURVIVAL Science & Technology - Other Topics medicine.symptom biological phenomena cell phenomena and immunity SRC Signal Transduction GROWTH-FACTOR Heterozygote Stromal cell Cell Survival In Vitro Techniques General Biochemistry Genetics and Molecular Biology Article Focal adhesion medicine Animals CANCER-CELLS Protein kinase B Paxillin Cell Proliferation Science & Technology Cell growth Endothelial Cells ADENOCARCINOMA General Chemistry ENDOTHELIAL-CELLS Vinculin TUBE FORMATION Focal Adhesion Kinase 1 biology.protein Mutant Proteins Proto-Oncogene Proteins c-akt Ex vivo |
| Zdroj: | Nature communications Kostourou, V, Lechertier, T, Reynolds, L E, Lees, D M, Baker, M, Jones, D T, Tavora, B, Ramjaun, A R, Birdsey, G M, Robinson, S D, Parsons, M, Randi, A M, Hart, I R & Hodivala-Dilke, K 2013, ' FAK-heterozygous mice display enhanced tumour angiogenesis ', Nature Communications, vol. 4, no. N/A, 2020 . https://doi.org/10.1038/ncomms3020 Scopus-Elsevier |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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