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. 2002 Oct;2(4):301-14.
doi: 10.1016/s1535-6108(02)00150-2.

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

Kimita Suyama  1 , Irina Shapiro, Mitchell Guttman, Rachel B Hazan
Affiliations
Free article

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

Kimita Suyama et al. Cancer Cell. 2002 Oct.
Free article

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.

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