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Cancer Cell. 2004 Jan;5(1):79-90.

Regulation of tumor angiogenesis by integrin-linked kinase (ILK).

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BC Cancer Agency, The Prostate Centre at Vancouver Hospital, and Department of Biochemistry and Molecular Biology, University of British Columbia, Jack Bell Research Center, 2660 Oak Street, Vancouver, BC, V6H 3Z6 Canada.


We show that integrin-linked kinase (ILK) stimulates the expression of VEGF by stimulating HIF-1alpha protein expression in a PKB/Akt- and mTOR/FRAP-dependent manner. In human prostate cancer cells, knockdown of ILK expression with siRNA, or inhibition of ILK activity, results in significant inhibition of HIF-1alpha and VEGF expression. In endothelial cells, VEGF stimulates ILK activity, and inhibition of ILK expression or activity results in the inhibition of VEGF-mediated endothelial cell migration, capillary formation in vitro, and angiogenesis in vivo. Inhibition of ILK activity also inhibits prostate tumor angiogenesis and suppresses tumor growth. These data demonstrate an important and essential role of ILK in two key aspects of tumor angiogenesis: VEGF expression by tumor cells and VEGF-stimulated blood vessel formation.

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