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Single-copy Snail upregulation causes partial epithelial-mesenchymal transition in colon cancer cells.

Accepted version
Peer-reviewed

Type

Article

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Authors

Tomic, Goran 
Kemp, Richard 
Winton, Doug J 

Abstract

BACKGROUND: Epithelial-mesenchymal transition (EMT) is an embryonic programme implicated in cancer stem cells, metastasis and therapeutic resistance. Its role in cancer progression remains controversial because the transition can be partial or complete in different models and contexts. METHODS: Using human colon cancer DLD-1 cells, we engineered a cell line with a single-copy of Snail that was doxycycline-inducible and compared it to existing EMT models in DLD-1. The effect of Snail upregulation was characterised functionally, morphologically, and by transcriptional profiling and protein expression. RESULTS: Induction with doxycycline increased Snail expression to a level similar to that observed in cancer cell lines spontaneously expressing Snail and results in partial EMT. In comparison, higher levels of overexpression arising from introduction of episomal-Snail, results in complete EMT. DLD-1 cells with partial EMT show chemoresistance in vitro, increased tumour growth in vivo and decreased apoptosis. CONCLUSIONS: These findings highlight that the amount of bioavailable Snail can dictate phenotypic outcome and that partial EMT may be a preferred outcome of models operating within a natural range of Snail overexpression.

Description

Keywords

Epithelial-mesenchymal transition, Metastasis, Partial transition, SNAIL, Humans, Cell Line, Tumor, Cell Movement, Colonic Neoplasms, Doxycycline, Epithelial-Mesenchymal Transition, Snail Family Transcription Factors, Up-Regulation

Journal Title

BMC Cancer

Conference Name

Journal ISSN

1471-2407
1471-2407

Volume Title

Publisher

BioMed Central
Sponsorship
Cancer Research UK (C14303/A17197)
Cancer Research UK (CB4230)
Wellcome Trust (103805/Z/14/Z)
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