Endothelial FAK is required for tumour angiogenesis

Bernardo Tavore; Silvia Batista; Louise.E Reynolds; Shalini Jadeja; Stephen Robinson; Vassiliki Koutourou; Ian Hart; Marcus Fruttiger; Maddy Parsons; Kairbaan M Holdivala-Dilke

doi:10.1002/emmm.201000106

Endothelial FAK is required for tumour angiogenesis

Bernardo Tavore, Silvia Batista, Louise.E Reynolds, Shalini Jadeja, Stephen Robinson, Vassiliki Koutourou, Ian Hart, Marcus Fruttiger, Maddy Parsons, Kairbaan M Holdivala-Dilke

Research output: Contribution to journal › Article › peer-review

117 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	516 - 528
Number of pages	13
Journal	EMBO Molecular Medicine
Volume	2
Issue number	12
DOIs	https://doi.org/10.1002/emmm.201000106
Publication status	Published - Dec 2010

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http://onlinelibrary.wiley.com/doi/10.1002/emmm.201000106/abstract

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@article{fb8a2097f72a432cbe0fd0ac025281a8,

title = "Endothelial FAK is required for tumour angiogenesis",

abstract = "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.",

author = "Bernardo Tavore and Silvia Batista and Louise.E Reynolds and Shalini Jadeja and Stephen Robinson and Vassiliki Koutourou and Ian Hart and Marcus Fruttiger and Maddy Parsons and Holdivala-Dilke, {Kairbaan M}",

year = "2010",

month = dec,

doi = "10.1002/emmm.201000106",

language = "English",

volume = "2",

pages = "516 -- 528",

journal = "EMBO Molecular Medicine",

publisher = "Wiley-Blackwell",

number = "12",

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TY - JOUR

T1 - Endothelial FAK is required for tumour angiogenesis

AU - Tavore, Bernardo

AU - Batista, Silvia

AU - Reynolds, Louise.E

AU - Jadeja, Shalini

AU - Robinson, Stephen

AU - Koutourou, Vassiliki

AU - Hart, Ian

AU - Fruttiger, Marcus

AU - Parsons, Maddy

AU - Holdivala-Dilke, Kairbaan M

PY - 2010/12

Y1 - 2010/12

N2 - 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.

AB - 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.

U2 - 10.1002/emmm.201000106

DO - 10.1002/emmm.201000106

M3 - Article

VL - 2

SP - 516

EP - 528

JO - EMBO Molecular Medicine

JF - EMBO Molecular Medicine

IS - 12

ER -

Endothelial FAK is required for tumour angiogenesis

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