Signaling through Raf-1 in the neovasculature and target validation by nanoparticles

Mol Cancer. 2003 Jul 30:2:27. doi: 10.1186/1476-4598-2-27.

Abstract

A recent study demonstrated that vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) activate Raf-1 kinase in an experimental neovasculature system. The study showed that bFGF and VEGF activate p21-activated protein kinase-1 (PAK-1) and Src kinase, respectively. PAK-1 and Src kinases phosphorylate specific serine and tyrosine residues within the activation loop of Raf-1 kinase. Their findings further suggest that phosphorylation at these sites protects endothelial cells from apoptosis induced by both intrinsic and extrinsic factors. The tumor neovasculature provides specific molecular markers or "zip codes". This group of investigators has previously shown that nanosphere-aided targeting of the neovasculature with mutant Raf-1 causes regression of the tumor vasculature. Thus, nanoparticles coated with "zip code"-specific homing biomolecules may be useful for delivering anti-angiogenic molecules that can induce tumor regression.

Publication types

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

MeSH terms

  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Fibroblast Growth Factor 2 / metabolism
  • Nanostructures*
  • Neovascularization, Physiologic*
  • Proto-Oncogene Proteins c-raf / genetics
  • Proto-Oncogene Proteins c-raf / metabolism*
  • Signal Transduction*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Proto-Oncogene Proteins c-raf