The Role of N-Cadherin in Breast Cancer Metastasis
Abstract
The intracellular signaling events that cause 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 the metastatic signaling cascade that is activated by N-cadherin and FGF-2 in breast tumor cells. In the presence of N-cadherin, FGF-2 caused a 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 downregulation, resulting in the accumulation of FGFR at the cell surface. Association of FGFR with N-cadherin was mediated by the first two Ig-like domains of FGFR. These results suggest that protection of the FGFR from ligand-induced degradation by N-cadherin enhances receptor signaling and provides a mechanism by which tumor cells acquire metastatic properties.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA405241
Entities
People
- Rachel Hazan
Organizations
- Icahn School of Medicine at Mount Sinai