RT Journal Article
SR Electronic
T1 Enhanced cell-cell contact stability and decreased N-cadherin-mediated migration upon Fibroblast Growth Factor Receptor-N-cadherin cross-talk
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 465930
DO 10.1101/465930
A1 Thao Nguyen
A1 Laurence Duchesne
A1 Gautham Hari Narayana Sankara Narayana
A1 Nicole Boggetto
A1 David D. Fernig
A1 Chandrashekhar Uttamrao Murade
A1 Benoit Ladoux
A1 René-Marc Mège
YR 2019
UL http://biorxiv.org/content/early/2019/06/17/465930.abstract
AB 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 feedback loop between N-cadherin and FGFR at adhesion sites limiting N-cadherin-based single cell migration.FGFFibroblast Growth FactorFGFRFibroblast Growth Factor ReceptorFPFluorescent ProteinFNFibronectinFRAPFluorescence Recovery After PhotobleachingGFPGreen Fluorescent ProteinNcadN-cadherinPBSPhosphate Buffer SalineRTKReceptor Tyrosine KinaseSEMStandard Error of the Mean