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 β-catenin at cell membranes and a reduction of expression of β-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 β-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.

Flow cytometry has recently become a very important tool in the study of the mechanisms of multidrug resistance (MDR). This technique allows rapid access to information regarding two characteristics related to the MDR phenotype: i) the level of overexpression of the P-glycoprotein; and ii) its functional aspect in expulsion of the cytotoxic agents to which the cell is exposed. In pharmacology, flow cytometry also allows evaluation of the capacity of modulating agents to reverse this resistance, and contributes a deeper insight into the mechanism of action of new molecules.

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