Subject(s)
Arthralgia/pathology , Arthritis, Infectious/diagnosis , Diabetes Mellitus, Type 1/physiopathology , Knee Joint/pathology , Lyme Disease/diagnosis , Nails, Ingrown/pathology , Arthralgia/microbiology , Arthritis, Infectious/drug therapy , Arthritis, Infectious/surgery , Child , Diagnosis, Differential , Diagnostic Errors , Enzyme-Linked Immunosorbent Assay , Female , Fever , Humans , Knee Joint/microbiology , Lyme Disease/drug therapy , Nails, Ingrown/complications , Nails, Ingrown/microbiology , Unnecessary ProceduresABSTRACT
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.