N-CAM Modulates Tumour-Cell Adhesion to Matrix by Inducing FGF-receptor Signalling

Nat Cell Biol. 2001 Jul;3(7):650-7. doi: 10.1038/35083041.

Abstract

Loss of expression of neural cell-adhesion molecule (N-CAM) is implicated in the progression of tumour metastasis. Here we show that N-CAM modulates neurite outgrowth and matrix adhesion of beta-cells from pancreatic tumours by assembling a fibroblast-growth-factor receptor-4 (FGFR-4) signalling complex, which consists of N-cadherin, FGFR-4, phospholipase C gamma (PLC-gamma), the adaptor protein FRS2, pp60(c-src), cortactin and growth-associated protein-43 (GAP-43). Dominant-negative FGFR-4, inhibitors of FGFR signalling and anti-beta(1)-integrin antibodies repress matrix adhesion induced by N-CAM. FGF ligands can replace N-CAM in promoting matrix adhesion but not neurite outgrowth. The results indicate that N-CAM stimulates beta1-integrin-mediated cell-matrix adhesion by activating FGFR signalling. This is a potential mechanism for preventing the dissemination of metastatic tumour cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion / drug effects
  • Extracellular Matrix / metabolism*
  • Integrin beta1 / pharmacology
  • Ligands
  • Mice
  • Neoplasm Metastasis / prevention & control
  • Neural Cell Adhesion Molecules / pharmacology*
  • Neurites / drug effects
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / secondary
  • Receptor, Fibroblast Growth Factor, Type 4
  • Receptors, Fibroblast Growth Factor / drug effects
  • Receptors, Fibroblast Growth Factor / physiology*
  • Signal Transduction / drug effects*
  • Tumor Cells, Cultured / physiology

Substances

  • Integrin beta1
  • Ligands
  • Neural Cell Adhesion Molecules
  • Receptors, Fibroblast Growth Factor
  • Fgfr4 protein, mouse
  • Receptor, Fibroblast Growth Factor, Type 4