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Ecotropic viral integration site 1 promotes metastasis independent of epithelial mesenchymal transition in colon cancer cells
The most indecipherable component of solid cancer is the development of metastasis which accounts for more than 90% of cancer-related mortalities. A developmental program termed epithelial-mesenchymal transition (EMT) has also been shown to play a critical role in promoting metastasis in epithelium-...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833819/ https://www.ncbi.nlm.nih.gov/pubmed/29339729 http://dx.doi.org/10.1038/s41419-017-0036-1 |
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author | Nayak, Kasturi Bala Sajitha, I. S. Kumar, T. R. Santhosh Chakraborty, Soumen |
author_facet | Nayak, Kasturi Bala Sajitha, I. S. Kumar, T. R. Santhosh Chakraborty, Soumen |
author_sort | Nayak, Kasturi Bala |
collection | PubMed |
description | The most indecipherable component of solid cancer is the development of metastasis which accounts for more than 90% of cancer-related mortalities. A developmental program termed epithelial-mesenchymal transition (EMT) has also been shown to play a critical role in promoting metastasis in epithelium-derived solid tumors. By analyzing publicly available microarray datasets, we observed that ecotropic viral integration site 1 (EVI1) correlates negatively with SLUG, a master regulator of EMT. This correlation was found to be relevant as we demonstrated that EVI1 binds to SLUG promoter element directly through the distal set of zinc fingers and downregulates its expression. Many studies have shown that the primary role of SLUG during EMT and EMT-like processes is the regulation of cell motility in most of the cancer cells. Knockdown of EVI1 in metastatic colon cancer cell and subsequent passage through matrigel not only increased the invading capacity but also induced an EMT-like morphological feature of the cells, such as spindle-shaped appearance and led to a significant reduction in the expression of the epithelial marker, E-CADHERIN and increase in the expression of the mesenchymal marker, N-CADHERIN. The cells, when injected into immunocompromised mice, failed to show any metastatic foci in distant organs however the ones with EVI1, metastasized in the intraperitoneal layer and also showed multiple micro metastatic foci in the lungs and spleen. These findings suggest that in colon cancer EVI1 is dispensable for epithelial-mesenchymal transition, however, is required for metastasis. |
format | Online Article Text |
id | pubmed-5833819 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-58338192018-03-06 Ecotropic viral integration site 1 promotes metastasis independent of epithelial mesenchymal transition in colon cancer cells Nayak, Kasturi Bala Sajitha, I. S. Kumar, T. R. Santhosh Chakraborty, Soumen Cell Death Dis Article The most indecipherable component of solid cancer is the development of metastasis which accounts for more than 90% of cancer-related mortalities. A developmental program termed epithelial-mesenchymal transition (EMT) has also been shown to play a critical role in promoting metastasis in epithelium-derived solid tumors. By analyzing publicly available microarray datasets, we observed that ecotropic viral integration site 1 (EVI1) correlates negatively with SLUG, a master regulator of EMT. This correlation was found to be relevant as we demonstrated that EVI1 binds to SLUG promoter element directly through the distal set of zinc fingers and downregulates its expression. Many studies have shown that the primary role of SLUG during EMT and EMT-like processes is the regulation of cell motility in most of the cancer cells. Knockdown of EVI1 in metastatic colon cancer cell and subsequent passage through matrigel not only increased the invading capacity but also induced an EMT-like morphological feature of the cells, such as spindle-shaped appearance and led to a significant reduction in the expression of the epithelial marker, E-CADHERIN and increase in the expression of the mesenchymal marker, N-CADHERIN. The cells, when injected into immunocompromised mice, failed to show any metastatic foci in distant organs however the ones with EVI1, metastasized in the intraperitoneal layer and also showed multiple micro metastatic foci in the lungs and spleen. These findings suggest that in colon cancer EVI1 is dispensable for epithelial-mesenchymal transition, however, is required for metastasis. Nature Publishing Group UK 2018-01-16 /pmc/articles/PMC5833819/ /pubmed/29339729 http://dx.doi.org/10.1038/s41419-017-0036-1 Text en © The Author(s) 2018 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Nayak, Kasturi Bala Sajitha, I. S. Kumar, T. R. Santhosh Chakraborty, Soumen Ecotropic viral integration site 1 promotes metastasis independent of epithelial mesenchymal transition in colon cancer cells |
title | Ecotropic viral integration site 1 promotes metastasis independent of epithelial mesenchymal transition in colon cancer cells |
title_full | Ecotropic viral integration site 1 promotes metastasis independent of epithelial mesenchymal transition in colon cancer cells |
title_fullStr | Ecotropic viral integration site 1 promotes metastasis independent of epithelial mesenchymal transition in colon cancer cells |
title_full_unstemmed | Ecotropic viral integration site 1 promotes metastasis independent of epithelial mesenchymal transition in colon cancer cells |
title_short | Ecotropic viral integration site 1 promotes metastasis independent of epithelial mesenchymal transition in colon cancer cells |
title_sort | ecotropic viral integration site 1 promotes metastasis independent of epithelial mesenchymal transition in colon cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833819/ https://www.ncbi.nlm.nih.gov/pubmed/29339729 http://dx.doi.org/10.1038/s41419-017-0036-1 |
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