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

Clara Tan; Severine Cruet-Hennequart; Armelle Troussard; Ladan Fazli; Penny Costello; Kym Sutton; Jeff Wheeler; Martin Gleave; Jasbinder Sanghera; Shoukat Dedhar

doi:10.1016/s1535-6108(03)00281-2

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

Cancer Cell. 2004 Jan;5(1):79-90. doi: 10.1016/s1535-6108(03)00281-2.

Authors

Clara Tan¹, Severine Cruet-Hennequart, Armelle Troussard, Ladan Fazli, Penny Costello, Kym Sutton, Jeff Wheeler, Martin Gleave, Jasbinder Sanghera, Shoukat Dedhar

Affiliation

¹ 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.

PMID: 14749128
DOI: 10.1016/s1535-6108(03)00281-2

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3-Phosphoinositide-Dependent Protein Kinases
Animals
Cell Movement / physiology
Chick Embryo
Endothelial Cells / metabolism*
Enzyme Inhibitors / pharmacology
Fish Proteins
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
Neovascularization, Pathologic / physiopathology*
PTEN Phosphohydrolase
Protein Kinases / metabolism
Protein Serine-Threonine Kinases / metabolism*
Protein Tyrosine Phosphatases / metabolism
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases
Transcription Factors / metabolism*
Tumor Cells, Cultured
Vascular Endothelial Growth Factor A / metabolism*

Substances

Enzyme Inhibitors
Fish Proteins
HIF1A protein, human
Hypoxia-Inducible Factor 1, alpha Subunit
Proto-Oncogene Proteins
Transcription Factors
Vascular Endothelial Growth Factor A
Protein Kinases
integrin-linked kinase
MTOR protein, human
3-Phosphoinositide-Dependent Protein Kinases
AKT1 protein, human
Protein Serine-Threonine Kinases
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases
Protein Tyrosine Phosphatases
PTEN Phosphohydrolase
Pten protein, pufferfish