N-cadherin adhesion has been reported to enhance cancer and neuronal cell migration either by mediating actomyosin-based force transduction or initiating fibroblast growth factor receptor (FGFR)-dependent biochemical signalling. Here we show that FGFR1 reduces N-cadherin-mediated cell migration. Both proteins are co-stabilised 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 stabilisation of cell adhesions require the FGFR activity stimulated by N-cadherin engagement. FGFR1 stabilises N-cadherin at the cell membrane through a pathway involving Src and p120. Moreover, FGFR1 stimulates the anchoring of N-cadherin to actin. We found that the migratory behaviour 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.
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This work was supported by grants from the CNRS, ARC foundation (contract number: PJA 20151203185), Human Frontier Science Program (HFSP grant RPG0040/2012), European Research Council under the European Union’s Seventh Framework Program (FP7/2007–2013)/ERC grant agreements n° 617233 (BL), Agence Nationale de la Recherche (ANR 2010 Blan1515) and NUS-USPC exchange program. TN was supported by a HFSP grant RPG0040/2012, then by Fondation pour la Recherche Médicale and Labex WhoAmI. We would like also to thank all present and past members of the Cell Adhesion & Mechanics lab at the Institute Jacques Monod for constant support and exchange. We thank Region Ile de France (E539) and Ligue contre le Cancer (R03/75–79) for the acquisition of the equipment. We thank CUM and M. Yao for held with magnetic tweezer experiment. CUM was supported by Fondation pour la Recherche Médicale (FDT20150532600), LD by the Association pour la Recherche contre le Cancer (Fondation ARC, P2009 CDD POST-DOC) and DDF by North West Cancer and the Cancer and Polio Research Fund. We thank O.Thoumine and R. Horwitz for their kind gift of NcadAAA and FGFR1 encoding plasmids, respectively. We acknowledge the ImagoSeine core facility of the Institut Jacques Monod, member of IBiSA and France-BioImaging (ANR-10-INBS-04) infrastructures.
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Nguyen, T., Duchesne, L., Sankara Narayana, G.H.N. et al. Enhanced cell–cell contact stability and decreased N-cadherin-mediated migration upon fibroblast growth factor receptor-N-cadherin cross talk. Oncogene 38, 6283–6300 (2019). https://doi.org/10.1038/s41388-019-0875-6
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