The c-Fes protein tyrosine kinase as a potential anti-angiogenic target in cancer

Front Biosci (Landmark Ed). 2011 Jan 1;16:1024-35. doi: 10.2741/3732.


Angiogenesis is implicated in many pathological conditions, including cancer progression. Novel approaches have enabled an understanding of how endothelial cellular processes are regulated in vivo during angiogenesis. Key players in angiogenesis are vascular endothelial growth factors (VEGFs) and Notch ligands. However, mechanisms of angiogenic responses by other proangiogenic factors in vivo are largely unknown. Research using cultured endothelial cells has shown that c-Fes is involved in the activation of phosphoinositide 3-kinase (PI3-kinase) downstream of a variety of cytokine receptors. The PI3-kinase/c-Akt pathway regulates cell survival, migration, and morphological differentiation of endothelial cells during angiogenesis, and c-Fes thus may be a potential target of anti-cancer therapy, especially for patients with anti-VEGF refractory cancer. In addition, a number of experiments have shown that a bone marrow-derived monocytic lineage regulates angiogenesis, and c-Fes is also expressed in these cells. Roles for c-Fes during angiogenesis will be the focus of extensive research in the future.

Publication types

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

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Angiopoietins / physiology
  • Chemokine CXCL12 / physiology
  • Endothelial Cells / physiology
  • Fibroblast Growth Factors / physiology
  • Humans
  • Interleukin-8 / physiology
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / pathology
  • Proto-Oncogene Proteins c-fes / drug effects*
  • Vascular Endothelial Growth Factor A / physiology
  • Vascular Endothelial Growth Factor Receptor-2 / physiology


  • Angiogenesis Inhibitors
  • Angiopoietins
  • Chemokine CXCL12
  • Interleukin-8
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factors
  • Vascular Endothelial Growth Factor Receptor-2
  • Proto-Oncogene Proteins c-fes