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Oncogene ; 38(35): 6283-6300, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31312021

RESUMO

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.


Assuntos
Caderinas/metabolismo , Comunicação Celular/fisiologia , Movimento Celular/fisiologia , Receptor Cross-Talk/fisiologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Actinas/metabolismo , Animais , Adesão Celular/fisiologia , Membrana Celular/metabolismo , Células Cultivadas , Células HEK293 , Humanos , Camundongos , Estabilidade Proteica , Transdução de Sinais/fisiologia , Junções Íntimas/fisiologia
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