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

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

Abstract

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.

Citation

Asiri, A., Toss, M. S., Raposo, T. P., Akhlaq, M., Thorpe, H., Alfahed, A., …Ilyas, M. (2019). Cten promotes Epithelial–Mesenchymal Transition (EMT) in colorectal cancer through stabilisation of Src. Pathology International, 69(7), 381-391. https://doi.org/10.1111/pin.12811

• Journal Article Type: Article
• Acceptance Date: May 3, 2019
• Online Publication Date: Jul 9, 2019
• Publication Date: Jul 9, 2019
• Deposit Date: Jul 20, 2019
• Publicly Available Date: Jul 10, 2020
• Journal: Pathology International
• Print ISSN: 1320-5463
• Electronic ISSN: 1440-1827
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 69
• Issue: 7
• Pages: 381-391
• DOI: https://doi.org/10.1111/pin.12811
• Keywords: Pathology and Forensic Medicine; General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/2319829
• Publisher URL: https://onlinelibrary.wiley.com/doi/full/10.1111/pin.12811
• Additional Information: This is the peer reviewed version of the following article: Cten promotes Epithelial-Mesenchymal Transition (EMT) in colorectal cancer through stabilization of Src, Abdulaziz Asiri, Michael S Toss, Teresa Pereira Raposo, Maham Akhlaq, Hannah Thorpe, Abdulaziz Alfahed , Abutaleb Asiri, Mohammad Ilyas, Pathology International, which has been published in final form at https://doi.org/10.1111/pin.12811. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
• Contract Date: Jul 20, 2019