The β3-integrin endothelial adhesome regulates microtubule-dependent cell migration

EMBO Rep. 2018 Jul;19(7):e44578. doi: 10.15252/embr.201744578. Epub 2018 May 24.

Abstract

Integrin β3 is seen as a key anti-angiogenic target for cancer treatment due to its expression on neovasculature, but the role it plays in the process is complex; whether it is pro- or anti-angiogenic depends on the context in which it is expressed. To understand precisely β3's role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the β3-dependent adhesome. We show that depletion of β3-integrin in this cell type leads to changes in microtubule behaviour that control cell migration. β3-integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2-driven control of active Rac1 localisation. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when β3-integrin levels are reduced.

Keywords: adhesome; endothelial; integrins; microtubules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A2 / genetics
  • Cell Adhesion / genetics*
  • Cell Movement / genetics*
  • Chromosomal Proteins, Non-Histone / genetics
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Endothelium, Vascular
  • Gene Expression Regulation / genetics
  • Humans
  • Integrin beta3 / genetics*
  • Mass Spectrometry
  • Mice
  • Microtubules / genetics
  • Microtubules / pathology
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / pathology
  • rac1 GTP-Binding Protein / genetics

Substances

  • ANXA2 protein, human
  • Annexin A2
  • Chromosomal Proteins, Non-Histone
  • Integrin beta3
  • Rcc2 protein, mouse
  • rac1 GTP-Binding Protein