Specific Oncogenic Activity of the Src-Family Tyrosine Kinase c-Yes in Colon Carcinoma Cells.

Florence Sancier (1) , Aurélie Dumont (1) , Audrey Sirvent (2) , Ludmilla Paquay de Plater (1) , Thomas Edmonds (1) , Géraldine David (1) , Michel Jan (1) , Catherine de Montrion (1) , Francis Cogé (1) , Stéphane Léonce (1) , Michael Burbridge (1) , Alain Bruno (1) , Jean A Boutin (1) , Brian Lockhart (1) , Serge Roche (2) , Francisco Cruzalegui (1)

1 Institut de Recherches Servier
2 CRBM - Centre de recherche en Biologie Cellulaire

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.

Domaines: Biochimie, Biologie Moléculaire

Florence Sancier, Aurélie Dumont, Audrey Sirvent, Ludmilla Paquay de Plater, Thomas Edmonds, et al.. Specific Oncogenic Activity of the Src-Family Tyrosine Kinase c-Yes in Colon Carcinoma Cells.. PLoS ONE, 2011, 6 (2), pp.e17237. ⟨10.1371/journal.pone.0017237⟩. ⟨hal-00581348⟩