Paxillin controls endothelial cell migration and tumor angiogenesis by altering neuropilin 2 expression

J Cell Sci. 2014 Apr 15;127(Pt 8):1672-83. doi: 10.1242/jcs.132316. Epub 2014 Feb 12.


Although a number of growth factors and receptors are known to control tumor angiogenesis, relatively little is known about the mechanism by which these factors influence the directional endothelial cell migration required for cancer microvessel formation. Recently, it has been shown that the focal adhesion protein paxillin is required for directional migration of fibroblasts in vitro. Here, we show that paxillin knockdown enhances endothelial cell migration in vitro and stimulates angiogenesis during normal development and in response to tumor angiogenic factors in vivo. Paxillin produces these effects by decreasing expression of neuropilin 2 (NRP2). Moreover, soluble factors secreted by tumors that stimulate vascular ingrowth, including vascular endothelial growth factor (VEGF), also decrease endothelial cell expression of paxillin and NRP2, and overexpression of NRP2 reverses these effects. These results suggest that the VEGF-paxillin-NRP2 pathway could represent a new therapeutic target for cancer and other angiogenesis-related diseases.

Keywords: Angiogenesis; Cancer; Capillary endothelial cell; Motility; Neuropilin 2; Paxillin; VEGF.

Publication types

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

MeSH terms

  • Animals
  • Carcinoma, Lewis Lung / blood supply
  • Carcinoma, Lewis Lung / metabolism
  • Carcinoma, Lewis Lung / pathology
  • Cell Line, Tumor
  • Cell Movement*
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Human Umbilical Vein Endothelial Cells / physiology*
  • Human Umbilical Vein Endothelial Cells / transplantation
  • Humans
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / metabolism*
  • Neuropilin-2 / genetics*
  • Neuropilin-2 / metabolism
  • Paxillin / physiology*
  • Retinal Vessels / physiopathology
  • Vascular Endothelial Growth Factor A / physiology


  • Neuropilin-2
  • PXN protein, human
  • Paxillin
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • neuropilin-2, human