HGF/scatter factor selectively promotes cell invasion by increasing integrin avidity

L. Trusolino, S. Cavassa, P. Angelini, M. Ando, A. Bertotti, P. M. Comoglio, C. Boccaccio

Research output: Contribution to journalArticle

Abstract

Hepatocyte growth factor/scatter factor (HGF/SF) controls a genetic program known as 'invasive growth', which involves as critical steps cell adhesion, migration, and trespassing of basement membranes. We show here that in MDA-MB-231 carcinoma cells, these steps are elicited by HGF/SF but not by epidermal growth factor (EGF). Neither factor substantially alters the production or activity of extracellular matrix proteases. HGF/SF, but not EGF, selectively promotes cell adhesion on laminins 1 and 5, fibronectin, and vitronectin through a P13-K-dependent mechanism. Increased adhesion is followed by enhanced invasiveness through isolated matrix proteins as well as through reconstituted basement membranes. Inhibition assays using function-blocking antibodies show that tiffs phenomenon is mediated by multiple integrins including β1, β3, β4, and β5. HGF/SF triggers clustering of all these integrins at actin-rich adhesive sites and lamellipodia but does not quantitatively modify their membrane expression. These data suggest that HGF/SF promotes cell adhesion and invasiveness by increasing the avidity of integrins for their specific ligands.

Original languageEnglish
Pages (from-to)1629-1640
Number of pages12
JournalFASEB Journal
Volume14
Issue number11
Publication statusPublished - 2000

Keywords

  • Adhesion
  • Growth factors
  • Integrin activation
  • MET
  • Tyrosine kinase receptors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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