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.

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 Tyrosine Phosphatases / metabolism
  • Protein-Serine-Threonine Kinases / 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
  • TOR Serine-Threonine Kinases
  • 3-Phosphoinositide-Dependent Protein Kinases
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Protein Tyrosine Phosphatases
  • PTEN Phosphohydrolase
  • Pten protein, pufferfish