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

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

Authors

Hannah Thorpe hannah-thorpe@hotmail.co.uk

Abdulaziz Asiri msxaa21@nottingham.ac.uk

Maham Akhlaq maham.inaam@hotmail.com

Mohammad Ilyas mohammad.ilyas@nottingham.ac.uk



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.

Journal Article Type Article
Journal Molecular Carcinogenesis
Print ISSN 0899-1987
Electronic ISSN 1098-2744
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 56
Issue 12
APA6 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), doi:10.1002/mc.22704
DOI https://doi.org/10.1002/mc.22704
Keywords Cten, Snail, migration, colorectal cancer, EMT
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
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf
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.wi...1002/mc.22704/abstract. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

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Thorpe manuscript.pdf (396 Kb)
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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