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

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 cel...

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Main Authors: Thorpe, Hannah, Asiri, Abdulaziz, Akhlaq, Maham, Ilyas, Mohammad
Format: Article
Published: Wiley 2017
Subjects:
Online Access:https://eprints.nottingham.ac.uk/44872/
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author Thorpe, Hannah
Asiri, Abdulaziz
Akhlaq, Maham
Ilyas, Mohammad
author_facet Thorpe, Hannah
Asiri, Abdulaziz
Akhlaq, Maham
Ilyas, Mohammad
author_sort Thorpe, Hannah
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-448722020-05-04T19:07:38Z https://eprints.nottingham.ac.uk/44872/ Cten promotes epithelial-mesenchymal transition through post-transcriptional stabilization of Snail Thorpe, Hannah Asiri, Abdulaziz Akhlaq, Maham Ilyas, Mohammad 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. Wiley 2017-09-18 Article PeerReviewed Thorpe, Hannah, Asiri, Abdulaziz, Akhlaq, Maham and Ilyas, Mohammad (2017) Cten promotes epithelial-mesenchymal transition through post-transcriptional stabilization of Snail. Molecular Carcinogenesis, 56 (12). pp. 2601-2609. ISSN 1098-2744 Cten Snail migration colorectal cancer EMT http://onlinelibrary.wiley.com/doi/10.1002/mc.22704/abstract doi:10.1002/mc.22704 doi:10.1002/mc.22704
spellingShingle Cten
Snail
migration
colorectal cancer
EMT
Thorpe, Hannah
Asiri, Abdulaziz
Akhlaq, Maham
Ilyas, Mohammad
Cten promotes epithelial-mesenchymal transition through post-transcriptional stabilization of Snail
title Cten promotes epithelial-mesenchymal transition through post-transcriptional stabilization of Snail
title_full Cten promotes epithelial-mesenchymal transition through post-transcriptional stabilization of Snail
title_fullStr Cten promotes epithelial-mesenchymal transition through post-transcriptional stabilization of Snail
title_full_unstemmed Cten promotes epithelial-mesenchymal transition through post-transcriptional stabilization of Snail
title_short Cten promotes epithelial-mesenchymal transition through post-transcriptional stabilization of Snail
title_sort cten promotes epithelial-mesenchymal transition through post-transcriptional stabilization of snail
topic Cten
Snail
migration
colorectal cancer
EMT
url https://eprints.nottingham.ac.uk/44872/
https://eprints.nottingham.ac.uk/44872/
https://eprints.nottingham.ac.uk/44872/