DOI: 10.1101/458109Oct 31, 2018Paper

The Cten signalling pathway stabilises Src protein to promote Epithelial-Mesenchymal Transition (EMT) in colorectal cancer

BioRxiv : the Preprint Server for Biology
Abdulaziz AsiriMohammad Ilyas


Cten is an oncogene which promotes epithelial-mesenchymal transition (EMT) in many signalling pathways. Having previously shown that Cten promotes EMT through Snail, we investigated whether Cten function could be mediated through Src (a known regulator of Snail). Cten levels were modulated by forced expression in colorectal cancer (CRC) cell lines with low Cten expression (HCT116 and RKO) and gene knockdown in a cell line with high Cten expression (SW620). In all cell lines, Cten was a positive regulator of Src expression. The functional importance of Src was tested by forcibly expressing Cten and simultaneously knocking down Src. This resulted in abrogation of Cten motility-inducing activity (cell migration, cell invasion, wound healing — each p<0.001) and abrogation of the promotion of colony formation by Cten (p<0.001) together with failure to induce the Cten targets — Snail and ROCK1. To complement these experiments, Cten expression was restored by forced expression in a subclone of SW620 in which the Cten gene had been deleted (SW620ΔCten). SW620ΔCten showed reduced expression of Src which increased following restoration of Cten by forced expression. In SW620ΔCten, restoration of Cten increased cell motility (cell migratio...Continue Reading

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