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Single-copy Snail upregulation causes partial epithelial-mesenchymal transition in colon cancer cells
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: Usin...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9926732/ https://www.ncbi.nlm.nih.gov/pubmed/36788501 http://dx.doi.org/10.1186/s12885-023-10581-3 |
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author | Junaid, Fatima Tomic, Goran Kemp, Richard Winton, Doug J. |
author_facet | Junaid, Fatima Tomic, Goran Kemp, Richard Winton, Doug J. |
author_sort | Junaid, Fatima |
collection | PubMed |
description | 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10581-3. |
format | Online Article Text |
id | pubmed-9926732 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-99267322023-02-15 Single-copy Snail upregulation causes partial epithelial-mesenchymal transition in colon cancer cells Junaid, Fatima Tomic, Goran Kemp, Richard Winton, Doug J. BMC Cancer Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10581-3. BioMed Central 2023-02-14 /pmc/articles/PMC9926732/ /pubmed/36788501 http://dx.doi.org/10.1186/s12885-023-10581-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Junaid, Fatima Tomic, Goran Kemp, Richard Winton, Doug J. Single-copy Snail upregulation causes partial epithelial-mesenchymal transition in colon cancer cells |
title | Single-copy Snail upregulation causes partial epithelial-mesenchymal transition in colon cancer cells |
title_full | Single-copy Snail upregulation causes partial epithelial-mesenchymal transition in colon cancer cells |
title_fullStr | Single-copy Snail upregulation causes partial epithelial-mesenchymal transition in colon cancer cells |
title_full_unstemmed | Single-copy Snail upregulation causes partial epithelial-mesenchymal transition in colon cancer cells |
title_short | Single-copy Snail upregulation causes partial epithelial-mesenchymal transition in colon cancer cells |
title_sort | single-copy snail upregulation causes partial epithelial-mesenchymal transition in colon cancer cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9926732/ https://www.ncbi.nlm.nih.gov/pubmed/36788501 http://dx.doi.org/10.1186/s12885-023-10581-3 |
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