Single-copy Snail upregulation causes partial epithelial-mesenchymal transition in colon cancer cells
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. Metho...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-023-10581-3 |
| _version_ | 1797864431013593088 |
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| author | Fatima Junaid Goran Tomic Richard Kemp Doug J. Winton |
| author_facet | Fatima Junaid Goran Tomic Richard Kemp Doug J. Winton |
| author_sort | Fatima Junaid |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T22:51:43Z |
| format | Article |
| id | doaj.art-728d7767cc444fe19eb270077470d5af |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-09T22:51:43Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-728d7767cc444fe19eb270077470d5af2023-03-22T11:35:27ZengBMCBMC Cancer1471-24072023-02-0123111010.1186/s12885-023-10581-3Single-copy Snail upregulation causes partial epithelial-mesenchymal transition in colon cancer cellsFatima Junaid0Goran Tomic1Richard Kemp2Doug J. Winton3Cancer Research UK – Cambridge Institute, University of CambridgeCancer Research UK – Cambridge Institute, University of CambridgeCancer Research UK – Cambridge Institute, University of CambridgeCancer Research UK – Cambridge Institute, University of CambridgeAbstract 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.https://doi.org/10.1186/s12885-023-10581-3Epithelial-mesenchymal transitionSNAILPartial transitionMetastasis |
| spellingShingle | Fatima Junaid Goran Tomic Richard Kemp Doug J. Winton Single-copy Snail upregulation causes partial epithelial-mesenchymal transition in colon cancer cells BMC Cancer Epithelial-mesenchymal transition SNAIL Partial transition Metastasis |
| 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 | Epithelial-mesenchymal transition SNAIL Partial transition Metastasis |
| url | https://doi.org/10.1186/s12885-023-10581-3 |
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