Premium
Cten promotes epithelial‐mesenchymal transition through the post‐transcriptional stabilization of Snail
Author(s) -
Thorpe Hannah,
Asiri Abdulaziz,
Akhlaq Maham,
Ilyas Mohammad
Publication year - 2017
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22704
Subject(s) - snail , biology , epithelial–mesenchymal transition , gene knockdown , motility , microbiology and biotechnology , snai1 , rna interference , metastasis , cell culture , cancer , genetics , rna , gene , ecology
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.