Cten promotes Epithelial-Mesenchymal Transition (EMT) in colorectal cancer through stabilisation of Src.

Abdulaziz Asiri, Michael S Toss, Teresa Pereira Raposo, Maham Akhlaq, Hannah Thorpe, Abdulaziz Alfahed, Abutaleb Asiri, Mohammad Ilyas

Pathology international 2019 Jul

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Cten is an oncogene promoting EMT in many signaling pathways, namely through Snail. We investigated whether Cten function could be mediated through Src. Cten levels were modulated by forced expression in HCT116 and gene knockdown in SW620 CRC (colorectal cancer) cell lines. In all cell lines, Cten was a positive regulator of Src expression. The functional importance of Src was tested by simultaneous Cten overexpression and Src knockdown. This resulted in abrogation of Cten motility-inducing activity and reduction of colony formation ability together with failure to induce Cten targets. In SW620ΔCten reduced Src expression increased following restoration of Cten, also leading to increased cell motility and colony formation, which were lost if Src was concomitantly knocked down. By qRT-PCR we showed modulation of Cten had no effect on Src mRNA. However, a CHX pulse chase assay demonstrated stabilization of Src protein by Cten. Finally, expression of Cten and Src was tested in a series of 84 primary CRCs and there was a significant correlation between them (P = 0.001). We conclude that Src is a novel and functionally important target of the Cten signaling pathway and that Cten protein causes post-transcriptional stabilization of Src in promoting EMT and possibly metastasis in CRC. © 2019 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Citation

Abdulaziz Asiri, Michael S Toss, Teresa Pereira Raposo, Maham Akhlaq, Hannah Thorpe, Abdulaziz Alfahed, Abutaleb Asiri, Mohammad Ilyas. Cten promotes Epithelial-Mesenchymal Transition (EMT) in colorectal cancer through stabilisation of Src. Pathology international. 2019 Jul;69(7):381-391