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

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

Etude de la stabilit d'un plasmide recombinant chez Bacillus subtilis

BSE B224617E / UCL - Université Catholique de LouvainSIGLEBEBelgiu

The Wnt3a targetome in triple-negative breast cancer cell lines

International audienc

Wnt3a-dependent gene repression in MDA-MB-468 and HCC38 cells.

<p>Venn diagrams indicate the number of genes that were down-regulated in MDA-MB-468 (A) or HCC38 cells (B) following Wnt3a stimulation for 6, 12 or 24 hours. Genes found in common in both cell lines are listed in the table and known Wnt target genes are shown bold (C).</p

Seventeen Wnt target genes up-regulated in HCC38 cells are strongly expressed in TNBC tumors and may reflect chronic activation of the Wnt signaling pathway.

<p>To identify potentially up-regulated Wnt target genes that could reflect the chronic activation of the Wnt pathway in human cancer, we selected the Wnt target genes that were up-regulated at both the earliest (6h) and the latest (24h) time points after the stimulation of HCC38 cells with Wnt3a. Of 133 genes up-regulated in Wnt3a-stimulated HCC38 cells at both time points, 72 genes were more strongly expressed in TNBC than in LA tumors (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122333#pone.0122333.s011" target="_blank">S6 Fig</a>). When we restricted our analysis to the most strongly deregulated genes (with a fold change > 1.3), 17 genes out of 72 genes were retained. The genes are ordered by their <i>P</i> value in the t-test for the TNBC subgroup. Rows: genes; columns: tumor samples. Red: more strongly expressed genes; blue: more poorly expressed genes.</p

Literature search for the 36 Wnt target genes (30 “up” and “6 down”) identified in both TNBC cell lines stimulated with Wnt3a for 6h.

<p>Literature search for the 36 Wnt target genes (30 “up” and “6 down”) identified in both TNBC cell lines stimulated with Wnt3a for 6h.</p