1. Academic Validation
  2. N-CAM modulates tumour-cell adhesion to matrix by inducing FGF-receptor signalling

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.
U Cavallaro 1 J Niedermeyer M Fuxa G Christofori
Affiliations

Affiliation

  • 1 Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
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.

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