HGF/SF Activation of Integrins

Figure 1. Following binding of HGF/SF, MET receptor signaling can modulate integrin function by promoting aggregation of integrins and adhesion to integrin-specific ligands.

Integrins and growth factor receptors can share common signaling pathways.1,2 Each type of receptor can impact the signal and ultimate response of the other. An example of a growth factor that has been shown to influence members of the integrin family of cell adhesion receptors is hepatocyte growth factor/scatter factor (HGF/SF). HGF/SF is a multifunctional cytokine that promotes mitogenesis, migration, invasion and morphogenesis (for a review, see reference 3). HGF/SF-dependent signaling modulates integrin function by promoting aggregation and cell adhesion.

Morphogenic responses to HGF/SF are dependent on adhesive events.1 HGF/SF-induced effects occur via signaling of the MET tyrosine kinase receptor, following ligand binding.4 HGF/SF binding to MET leads to enhanced integrin-mediated B cell and lymphoma cell adhesion.5, 6 Blocking experiments with monoclonal anti bodies directed against integrin subunits indicate that alpha4beta1 and alpha5beta1 integrins on hematopoietic progenitor cells are activated by HGF/SF to induce adhesion to fibronectin.7 The HGF/SF-dependent signal transduction pathway can also induce ligand-binding activity in functionally inactive alphavbeta3 integrins.8 Antibody blocking experiments with monoclonal antibodies generated against alphavbeta3 disrupt HGF/SF-induced alphavbeta3 enrichment at focal contacts and impairs epithelial cell adhesion. These effects elicited by HGF/SF highlight the importance of growth factor regulation of integrin function in both normal and tumor cells.

References

  1. Matsumoto, K. et al. (1995) Cancer Metastasis Rev. 14:205.
  2. Clark, E.A. and J.S. Brugge (1995) Science 268:233.
  3. Jiang, W.G. and S. Hiscox (1997) Histol. Histopathol. 2:537.
  4. Galimi, F. et al. (1993) Stem Cells (Dayt.) 2:22.
  5. Van der Voort, R. et al. (1997) J. Exp. Med. 185:2121.
  6. Weimar, I.S. et al. (1997) Blood 89:990.
  7. Weimar, I.S. et al. (1998) Experimental Hematol. 26:885.
  8. Trusolino, L. et al. (1998) J. Cell Biology 142:1145.