PURPOSE: Focal adhesion kinase (FAK) is involved in processes integral to angiogenesis, such as cell growth, survival, and migration. FAK is activated by angiogenic growth factors, such as insulin-like growth factor (IGF)-I, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF). The study was conducted to determine whether overexpression of FAK or FAK-related nonkinase (FRNK), an inhibitor of FAK, could influence human retinal endothelial cell (HREC) migration and in vivo angiogenesis. METHODS: Migration in response to a combination of growth factors was examined in transfected HRECs overexpressing FAK or FRNK. The effect of FAK or FRNK overexpression on preretinal neovascularization was examined in a mouse model of oxygen-induced retinopathy. RESULTS: Overexpression of FAK in HRECs resulted in a 102% +/- 13% increase (P = 1.4 x 10(-4)) in cell migration, whereas overexpression of FRNK resulted in a 20% +/- 8% decrease (P = 0.01). Overexpression of FAK in mouse eyes led to formation of numerous large vascular tufts resembling glomeruli and a 57% +/- 7% increase in preretinal neovascularization (P = 3 x 10(-9)), whereas FRNK resulted in a 55% +/- 15% reduction (P = 5 x 10(-5)). CONCLUSIONS: Modulating the FAK/FRNK system may provide a novel approach to inhibiting pathologic retinal angiogenesis.
PURPOSE:Focal adhesion kinase (FAK) is involved in processes integral to angiogenesis, such as cell growth, survival, and migration. FAK is activated by angiogenic growth factors, such as insulin-like growth factor (IGF)-I, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF). The study was conducted to determine whether overexpression of FAK or FAK-related nonkinase (FRNK), an inhibitor of FAK, could influence human retinal endothelial cell (HREC) migration and in vivo angiogenesis. METHODS: Migration in response to a combination of growth factors was examined in transfected HRECs overexpressing FAK or FRNK. The effect of FAK or FRNK overexpression on preretinal neovascularization was examined in a mouse model of oxygen-induced retinopathy. RESULTS: Overexpression of FAK in HRECs resulted in a 102% +/- 13% increase (P = 1.4 x 10(-4)) in cell migration, whereas overexpression of FRNK resulted in a 20% +/- 8% decrease (P = 0.01). Overexpression of FAK in mouse eyes led to formation of numerous large vascular tufts resembling glomeruli and a 57% +/- 7% increase in preretinal neovascularization (P = 3 x 10(-9)), whereas FRNK resulted in a 55% +/- 15% reduction (P = 5 x 10(-5)). CONCLUSIONS: Modulating the FAK/FRNK system may provide a novel approach to inhibiting pathologic retinal angiogenesis.
Authors: Jyotsnabaran Halder; Aparna A Kamat; Charles N Landen; Liz Y Han; Susan K Lutgendorf; Yvonne G Lin; William M Merritt; Nicholas B Jennings; Arturo Chavez-Reyes; Robert L Coleman; David M Gershenson; Rosemarie Schmandt; Steven W Cole; Gabriel Lopez-Berestein; Anil K Sood Journal: Clin Cancer Res Date: 2006-08-15 Impact factor: 12.531
Authors: Christina L Grant; Leslie A Caromile; Vivienne Ho; Khayyam Durrani; M Mamunur Rahman; Kevin P Claffey; Guo-Hua Fong; Linda H Shapiro Journal: PLoS One Date: 2012-07-18 Impact factor: 3.240
Authors: Jordan J Toutounchian; Jena J Steinle; Patrudu S Makena; Christopher M Waters; Matthew W Wilson; Barrett G Haik; Duane D Miller; Charles R Yates Journal: PLoS One Date: 2014-06-23 Impact factor: 3.240