The role of semaphorins and their receptors in vascular development and cancer

Exp Cell Res. 2013 May 15;319(9):1306-16. doi: 10.1016/j.yexcr.2013.02.003. Epub 2013 Feb 17.


Semaphorins (Semas) are a large family of traditional axon guidance molecules. Through interactions with their receptors, Plexins and Neuropilins, Semas play critical roles in a continuously growing list of diverse biological systems. In this review, we focus on their function in regulating vascular development. In addition, over the past few years a number of findings have shown the crucial role that Semas and their receptors play in the regulation of cancer progression and tumor angiogenesis. In particular, Semas control tumor progression by directly influencing the behavior of cancer cells or, indirectly, by modulating angiogenesis and the function of other cell types in the tumor microenvironment (i.e., inflammatory cells and fibroblasts). Some Semas can activate or inhibit tumor progression and angiogenesis, while others may have the opposite effect depending on specific post-translational modifications. Here we will also discuss the diverse biological effects of Semas and their receptor complexes on cancer progression as well as their impact on the tumor microenvironment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Adhesion Molecules / metabolism
  • Humans
  • Neoplasms / blood supply*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Physiologic
  • Nerve Tissue Proteins / metabolism
  • Neuropilins / metabolism
  • Semaphorins / physiology*
  • Signal Transduction
  • Tumor Microenvironment


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