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MMP1 expression is activated by Slug and enhances multi-drug resistance (MDR) in breast cancer
High matrix metalloproteinase 1 (MMP1) expression is associated with enhanced breast cancer growth and metastasis and also might predict poor prognosis. In this study, we further investigated the functional role of MMP1 and how it is upregulated in multi-drug resistant (MDR) breast cancer cells. By...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363985/ https://www.ncbi.nlm.nih.gov/pubmed/28334049 http://dx.doi.org/10.1371/journal.pone.0174487 |
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author | Shen, Ching-Ju Kuo, Yu-Ling Chen, Chien-Chung Chen, Ming-Jenn Cheng, Ya-Min |
author_facet | Shen, Ching-Ju Kuo, Yu-Ling Chen, Chien-Chung Chen, Ming-Jenn Cheng, Ya-Min |
author_sort | Shen, Ching-Ju |
collection | PubMed |
description | High matrix metalloproteinase 1 (MMP1) expression is associated with enhanced breast cancer growth and metastasis and also might predict poor prognosis. In this study, we further investigated the functional role of MMP1 and how it is upregulated in multi-drug resistant (MDR) breast cancer cells. By retrieving microarray data in GEO datasets and the survival data in the Kaplan Meier plotter, we observed that MMP1 is significantly upregulated in MCF-7/ADR cells compared to the parental MCF-7 cells, while high MMP1 expression is associated with worse overall survival (OS) and recurrence free survival (RFS) in breast cancer patients after systematic therapy. Functional studies showed that MMP1 overexpression significantly reduced the drug sensitivity in MCF-7 cells, while MMP1 knockdown substantially enhanced the sensitivity in MCF-7/ADR cells. By performing western blotting and immunofluorescent staining, we confirmed that MCF-7/ADR cells had enhanced mesenchymal properties than MCF-7 cells. In MCF-7 cells, enforced Slug expression resulted in significant MMP1 upregulation, while in MCF-7/ADR cells, Slug knockdown led to reduced MMP1 expression. By performing bioinformatic analysis, we observed that the promoter of MMP1 has three putative Slug binding sites. The following dual luciferase assay and ChIP-qPCR verified these three binding sites. Therefore, we infer that Slug enhances MMP1 transcription via directly binding to the promoter region in breast cancer cells, which is a previously unrecognized mechanism in the development of MDR. |
format | Online Article Text |
id | pubmed-5363985 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-53639852017-04-06 MMP1 expression is activated by Slug and enhances multi-drug resistance (MDR) in breast cancer Shen, Ching-Ju Kuo, Yu-Ling Chen, Chien-Chung Chen, Ming-Jenn Cheng, Ya-Min PLoS One Research Article High matrix metalloproteinase 1 (MMP1) expression is associated with enhanced breast cancer growth and metastasis and also might predict poor prognosis. In this study, we further investigated the functional role of MMP1 and how it is upregulated in multi-drug resistant (MDR) breast cancer cells. By retrieving microarray data in GEO datasets and the survival data in the Kaplan Meier plotter, we observed that MMP1 is significantly upregulated in MCF-7/ADR cells compared to the parental MCF-7 cells, while high MMP1 expression is associated with worse overall survival (OS) and recurrence free survival (RFS) in breast cancer patients after systematic therapy. Functional studies showed that MMP1 overexpression significantly reduced the drug sensitivity in MCF-7 cells, while MMP1 knockdown substantially enhanced the sensitivity in MCF-7/ADR cells. By performing western blotting and immunofluorescent staining, we confirmed that MCF-7/ADR cells had enhanced mesenchymal properties than MCF-7 cells. In MCF-7 cells, enforced Slug expression resulted in significant MMP1 upregulation, while in MCF-7/ADR cells, Slug knockdown led to reduced MMP1 expression. By performing bioinformatic analysis, we observed that the promoter of MMP1 has three putative Slug binding sites. The following dual luciferase assay and ChIP-qPCR verified these three binding sites. Therefore, we infer that Slug enhances MMP1 transcription via directly binding to the promoter region in breast cancer cells, which is a previously unrecognized mechanism in the development of MDR. Public Library of Science 2017-03-23 /pmc/articles/PMC5363985/ /pubmed/28334049 http://dx.doi.org/10.1371/journal.pone.0174487 Text en © 2017 Shen et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Shen, Ching-Ju Kuo, Yu-Ling Chen, Chien-Chung Chen, Ming-Jenn Cheng, Ya-Min MMP1 expression is activated by Slug and enhances multi-drug resistance (MDR) in breast cancer |
title | MMP1 expression is activated by Slug and enhances multi-drug resistance (MDR) in breast cancer |
title_full | MMP1 expression is activated by Slug and enhances multi-drug resistance (MDR) in breast cancer |
title_fullStr | MMP1 expression is activated by Slug and enhances multi-drug resistance (MDR) in breast cancer |
title_full_unstemmed | MMP1 expression is activated by Slug and enhances multi-drug resistance (MDR) in breast cancer |
title_short | MMP1 expression is activated by Slug and enhances multi-drug resistance (MDR) in breast cancer |
title_sort | mmp1 expression is activated by slug and enhances multi-drug resistance (mdr) in breast cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363985/ https://www.ncbi.nlm.nih.gov/pubmed/28334049 http://dx.doi.org/10.1371/journal.pone.0174487 |
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