Specific oncogenic activity of the Src-family tyrosine kinase c-Yes in colon carcinoma cells

• Published in: PloS one 2011-02, Vol.6 (2), p.e17237
• Main Authors: Sancier, Florence, Dumont, Aurélie, Sirvent, Audrey, Paquay de Plater, Ludmilla, Edmonds, Thomas, David, Géraldine, Jan, Michel, de Montrion, Catherine, Cogé, Francis, Léonce, Stéphane, Burbridge, Michael, Bruno, Alain, Boutin, Jean A, Lockhart, Brian, Roche, Serge, Cruzalegui, Francisco
• Format: Article
• Language: English
• Subjects: Agar; Animals; Apoptosis; Biochemistry, Molecular Biology; Biology; Breast cancer; Cancer metastasis; Carcinoma; Carcinoma - genetics; Carcinoma - pathology; Cell adhesion & migration; Cell Line, Tumor; Cell membranes; Cell migration; Cell Transformation, Neoplastic - genetics; Clustering; Colon; Colon cancer; Colonic Neoplasms - genetics; Colonic Neoplasms - pathology; Colorectal cancer; Deoxyribonucleic acid; Development and progression; Disease Progression; DNA; Female; Fibroblasts; Gene expression; Gene Knockdown Techniques; Gene silencing; HCT116 Cells; HT29 Cells; Humans; Inhibition; Kinases; Leukocyte migration; Life Sciences; Liver; Liver cancer; Medical prognosis; Medicine; Membranes; Metastases; Mice; Mice, Nude; Mice, SCID; Motility; Organ Specificity - genetics; Phenols (Class of compounds); Phosphorylation; Position (location); Protein-tyrosine kinase; Proteins; Proto-Oncogene Proteins c-yes - antagonists & inhibitors; Proto-Oncogene Proteins c-yes - genetics; Proto-Oncogene Proteins c-yes - physiology; Proto-Oncogene Proteins pp60(c-src) - genetics; Proto-Oncogene Proteins pp60(c-src) - physiology; Rodents; Signal transduction; Signal Transduction - genetics; Signal Transduction - physiology; Signaling; Src protein; src-Family Kinases - antagonists & inhibitors; src-Family Kinases - genetics; src-Family Kinases - physiology; Transplantation, Heterologous; Tyrosine; Vascular endothelial growth factor; Xenografts; β-Catenin
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0017237

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.