Assuntos
Artralgia/patologia , Artrite Infecciosa/diagnóstico , Diabetes Mellitus Tipo 1/fisiopatologia , Articulação do Joelho/patologia , Doença de Lyme/diagnóstico , Unhas Encravadas/patologia , Artralgia/microbiologia , Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/cirurgia , Criança , Diagnóstico Diferencial , Erros de Diagnóstico , Ensaio de Imunoadsorção Enzimática , Feminino , Febre , Humanos , Articulação do Joelho/microbiologia , Doença de Lyme/tratamento farmacológico , Unhas Encravadas/complicações , Unhas Encravadas/microbiologia , Procedimentos DesnecessáriosRESUMO
c-Yes, a member of the Src tyrosine kinase family, is found highly activated in colon carcinoma but its importance relative to c-Src has remained unclear. Here we show that, in HT29 colon carcinoma cells, silencing of c-Yes, but not of c-Src, selectively leads to an increase of cell clustering associated with a localisation of ß-catenin at cell membranes and a reduction of expression of ß-catenin target genes. c-Yes silencing induced an increase in apoptosis, inhibition of growth in soft-agar and in mouse xenografts, inhibition of cell migration and loss of the capacity to generate liver metastases in mice. Re-introduction of c-Yes, but not c -Src, restores transforming properties of c-Yes depleted cells. Moreover, we found that c-Yes kinase activity is required for its role in ß-catenin localisation and growth in soft agar, whereas kinase activity is dispensable for its role in cell migration. We conclude that c-Yes regulates specific oncogenic signalling pathways important for colon cancer progression that is not shared with c-Src.