Cten promotes epithelial-mesenchymal transition through post-transcriptional stabilization of Snail

Thorpe, Hannah; Asiri, Abdulaziz; Akhlaq, Maham; Ilyas, Mohammad

Abstract

Cten promotes cell migration however the knowledge of underlying signalling pathways is sparse. We have shown that Cten downregulates E-cadherin, a feature of epithelial to mesenchymal transition (EMT). This prompted us to investigate whether Cten further contributed to EMT processes to regulate cell motility.

The regulation of Snail by Cten was investigated following overexpression, knockdown (by RNA-interference) or knockout of Cten in HCT116, Caco-2 and SW620 colorectal cancer (CRC) cell lines. Subsequently, the cycloheximide (CHX) pulse chase assay was used to investigate changes in Snail protein stability and the functional relevance of Cten-Snail signalling was investigated.

Snail was identified as a downstream target of Cten signalling using multiple approaches of Cten expression manipulation. Furthermore, this activity was mediated through the SH2 domain of Cten. The CHX assay confirmed that Cten was regulating Snail at a post transcriptional level and this was through the prevention of Snail degradation. Cell migration, invasion and colony formation efficiency were increased following forced expression of GFP-Cten but subsequently lost when Snail was knocked down, demonstrating a functional Cten-Snail signalling axis.

In conclusion, we have described a novel Cten-Snail signaling pathway that contributes to cell motility in CRC, mediated by the stabilization of Snail protein. This finding potentially furthers the understanding of EMT regulatory networks in cancer metastasis.

Citation

Thorpe, H., Asiri, A., Akhlaq, M., & Ilyas, M. (in press). Cten promotes epithelial-mesenchymal transition through post-transcriptional stabilization of Snail. Molecular Carcinogenesis, 56(12), https://doi.org/10.1002/mc.22704

• Journal Article Type: Article
• Acceptance Date: Jul 7, 2017
• Online Publication Date: Sep 18, 2017
• Deposit Date: Aug 15, 2017
• Publicly Available Date: Sep 19, 2018
• Journal: Molecular Carcinogenesis
• Print ISSN: 0899-1987
• Electronic ISSN: 1098-2744
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 56
• Issue: 12
• DOI: https://doi.org/10.1002/mc.22704
• Keywords: Cten, Snail, migration, colorectal cancer, EMT
• Public URL: https://nottingham-repository.worktribe.com/output/883487
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1002/mc.22704/abstract
• Related Public URLs: http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1098-2744
• Additional Information: This is the peer reviewed version of the following article: Thorpe H, Asiri A, Akhlaq M, Ilyas M. Cten promotes epithelial-mesenchymal transition through post-transcriptional stabilization of Snail. Molecular Carcinogenesis. 2017;56:2601–2609. https://doi.org/10.1002/mc.22704 which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/mc.22704/abstract. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
• Contract Date: Aug 15, 2017