Enhanced cell-cell contact stability upon Fibroblast Growth factor Receptor/N-cadherin cross-talk

N-cadherin adhesion has been reported to enhance cancer and neuronal cell migration by mediating either actomyosin-based force transduction or initiating Fibroblast Growth Factor Receptor (FGFR)-dependent biochemical signaling. We show here that FGFR1 reduces N-cadherin-mediated cell migration. Both proteins are co-stabilized at cell-cell contacts through direct interaction. As a consequence, cell adhesion is strengthened limiting the migration of cells on N-cadherin. Both the inhibition of migration and the stabilization of cell adhesions require the FGFR activity stimulated by N-cadherin engagement. FGFR1 stabilizes N-cadherin at the cell membrane by decreasing its endocytosis through a pathway involving Src and p120. Moreover, FGFR1 stimulates the anchoring of N-cadherin to actin. We found that the migratory behavior of cells depends on an optimum balance between FGFR-regulated N-cadherin adhesion and actin dynamics. Based on these findings we propose a positive feed-back loop between N-cadherin and FGFR at adhesion sites limiting N-cadherin-based single cell migration.