Semaphorin signaling in angiogenesis, lymphangiogenesis and cancer

Cell Res. 2012 Jan;22(1):23-32. doi: 10.1038/cr.2011.198. Epub 2011 Dec 13.


Angiogenesis, the formation of new blood vessels from preexisting vasculature, is essential for many physiological processes, and aberrant angiogenesis contributes to some of the most prevalent human diseases, including cancer. Angiogenesis is controlled by delicate balance between pro- and anti-angiogenic signals. While pro-angiogenic signaling has been extensively investigated, how developmentally regulated, naturally occurring anti-angiogenic molecules prevent the excessive growth of vascular and lymphatic vessels is still poorly understood. In this review, we summarize the current knowledge on how semaphorins and their receptors, plexins and neuropilins, control normal and pathological angiogenesis, with an emphasis on semaphorin-regulated anti-angiogenic signaling circuitries in vascular and lymphatic endothelial cells. This emerging body of information may afford the opportunity to develop novel anti-angiogenic therapeutic strategies.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Cell Adhesion Molecules / metabolism
  • Endothelial Cells / metabolism
  • Humans
  • Lymphangiogenesis*
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology*
  • Neovascularization, Physiologic*
  • Nerve Tissue Proteins / metabolism
  • Neuropilins / metabolism
  • Semaphorins / metabolism*
  • Signal Transduction*


  • Cell Adhesion Molecules
  • Nerve Tissue Proteins
  • Neuropilins
  • Semaphorins
  • plexin