A signaling pathway leading to metastasis is controlled by N-cadherin and the FGF receptor

Kimita Suyama, Irina Shapiro, Mitchell Guttman, Rachel Hazan

Research output: Contribution to journalArticle

370 Citations (Scopus)

Abstract

The intracellular signaling events causing tumor cells to become metastatic are not well understood. N-cadherin and FGF-2 synergistically increase migration, invasion, and secretion of extracellular proteases in breast tumor cells. Here, we define a metastatic signaling cascade activated by N-cadherin and FGF-2. In the presence of N-cadherin, FGF-2 caused sustained activation of the MAPK-ERK pathway, leading to MMP-9 gene transcription and cellular invasion. N-cadherin prevented the FGF receptor (FGFR) from undergoing ligand-induced internalization, resulting in increased FGFR-1 stability. Association of FGFR-1 with N-cadherin was mediated by the first two Ig-like domains of FGFR-1. These results suggest that protection of the FGFR-1 from ligand-induced downregulation by N-cadherin enhances receptor signaling and provides a mechanism by which tumor cells can acquire metastatic properties.

Original languageEnglish (US)
Pages (from-to)301-314
Number of pages14
JournalCancer Cell
Volume2
Issue number4
DOIs
StatePublished - Oct 2002
Externally publishedYes

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Fibroblast Growth Factor Receptors
Cadherins
Neoplasm Metastasis
Fibroblast Growth Factor 1
Fibroblast Growth Factor 2
Ligands
MAP Kinase Signaling System
Matrix Metalloproteinases
Neoplasms
Peptide Hydrolases
Down-Regulation
Breast Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

A signaling pathway leading to metastasis is controlled by N-cadherin and the FGF receptor. / Suyama, Kimita; Shapiro, Irina; Guttman, Mitchell; Hazan, Rachel.

In: Cancer Cell, Vol. 2, No. 4, 10.2002, p. 301-314.

Research output: Contribution to journalArticle

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