Emerging role of semaphorins as major regulatory signals and potential therapeutic targets in cancer

Cancer Cell. 2012 Aug 14;22(2):145-52. doi: 10.1016/j.ccr.2012.06.031.


Semaphorins are mainly known as guidance signals in development, acting through receptors called Plexins. However, their role in cancer is rapidly emerging in the regulation of tumor angiogenesis, tumor growth, cancer cell invasiveness, and metastatic spreading. Intriguingly, activated plexins can transactivate receptor tyrosine kinases, such as MET, VEGFR2, FGFR2, and ERBB2, and lead to distinctive effects in a cell-context-dependent manner. Moreover, certain semaphorins concomitantly target endothelial and cancer cells, and can achieve remarkable inhibition of angiogenesis and tumor growth, associated with anti-metastatic activity. Altogether, these data validate the identification of semaphorin signals as promising therapeutic targets in cancer.

Publication types

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

MeSH terms

  • Animals
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Humans
  • Molecular Targeted Therapy*
  • Neoplasms / blood supply
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neovascularization, Pathologic / metabolism
  • Semaphorins / antagonists & inhibitors*
  • Semaphorins / metabolism*
  • Signal Transduction*


  • Semaphorins