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E. coli Secretome Metabolically Modulates MDA-MB-231 Breast Cancer Cells’ Energy Metabolism
Breast cancer (BC) is commonly diagnosed in women. BC cells are associated with altered metabolism, which is essential to support their energetic requirements, cellular proliferation, and continuous survival. The altered metabolism of BC cells is a result of the genetic abnormalities of BC cells. Ri...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9964955/ https://www.ncbi.nlm.nih.gov/pubmed/36835626 http://dx.doi.org/10.3390/ijms24044219 |
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author | AlMalki, Reem H. Sebaa, Rajaa Al-Ansari, Mysoon M. Al-Alwan, Monther Alwehaibi, Moudi A. Rahman, Anas M. Abdel |
author_facet | AlMalki, Reem H. Sebaa, Rajaa Al-Ansari, Mysoon M. Al-Alwan, Monther Alwehaibi, Moudi A. Rahman, Anas M. Abdel |
author_sort | AlMalki, Reem H. |
collection | PubMed |
description | Breast cancer (BC) is commonly diagnosed in women. BC cells are associated with altered metabolism, which is essential to support their energetic requirements, cellular proliferation, and continuous survival. The altered metabolism of BC cells is a result of the genetic abnormalities of BC cells. Risk factors can also enhance it, including age, lifestyle, hormone disturbances, etc. Other unknown BC-promoting risk factors are under scientific investigation. One of these investigated factors is the microbiome. However, whether the breast microbiome found in the BC tissue microenvironment can impact BC cells has not been studied. We hypothesized that E. coli, part of a normal breast microbiome with more presence in BC tissue, secretes metabolic molecules that could alter BC cells’ metabolism to maintain their survival. Thus, we directly examined the impact of the E. coli secretome on the metabolism of BC cells in vitro. MDA-MB-231 cells, an in vitro model of aggressive triple-negative BC cells, were treated with the E. coli secretome at different time points, followed by untargeted metabolomics analyses via liquid chromatography–mass spectrometry to identify metabolic alterations in the treated BC cell lines. MDA-MB-231 cells that were not treated were used as controls. Moreover, metabolomic analyses were performed on the E. coli secretome to profile the most significant bacterial metabolites affecting the metabolism of the treated BC cell lines. The metabolomics results revealed about 15 metabolites that potentially have indirect roles in cancer metabolism that were secreted from E. coli in the culture media of MDA-MB-231 cells. The cells treated with the E. coli secretome showed 105 dysregulated cellular metabolites compared to controls. The dysregulated cellular metabolites were involved in the metabolism of fructose and mannose, sphingolipids, amino acids, fatty acids, amino sugar, nucleotide sugar, and pyrimidine, which are vital pathways required for the pathogenesis of BC. Our findings are the first to show that the E. coli secretome modulates the BC cells’ energy metabolism, highlighting insights into the possibility of altered metabolic events in BC tissue in the actual BC tissue microenvironment that are potentially induced by the local bacteria. Our study provides metabolic data that could be as a basis for future studies searching for the underlying mechanisms mediated by bacteria and their secretome to alter the metabolism of BC cells. |
format | Online Article Text |
id | pubmed-9964955 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99649552023-02-26 E. coli Secretome Metabolically Modulates MDA-MB-231 Breast Cancer Cells’ Energy Metabolism AlMalki, Reem H. Sebaa, Rajaa Al-Ansari, Mysoon M. Al-Alwan, Monther Alwehaibi, Moudi A. Rahman, Anas M. Abdel Int J Mol Sci Article Breast cancer (BC) is commonly diagnosed in women. BC cells are associated with altered metabolism, which is essential to support their energetic requirements, cellular proliferation, and continuous survival. The altered metabolism of BC cells is a result of the genetic abnormalities of BC cells. Risk factors can also enhance it, including age, lifestyle, hormone disturbances, etc. Other unknown BC-promoting risk factors are under scientific investigation. One of these investigated factors is the microbiome. However, whether the breast microbiome found in the BC tissue microenvironment can impact BC cells has not been studied. We hypothesized that E. coli, part of a normal breast microbiome with more presence in BC tissue, secretes metabolic molecules that could alter BC cells’ metabolism to maintain their survival. Thus, we directly examined the impact of the E. coli secretome on the metabolism of BC cells in vitro. MDA-MB-231 cells, an in vitro model of aggressive triple-negative BC cells, were treated with the E. coli secretome at different time points, followed by untargeted metabolomics analyses via liquid chromatography–mass spectrometry to identify metabolic alterations in the treated BC cell lines. MDA-MB-231 cells that were not treated were used as controls. Moreover, metabolomic analyses were performed on the E. coli secretome to profile the most significant bacterial metabolites affecting the metabolism of the treated BC cell lines. The metabolomics results revealed about 15 metabolites that potentially have indirect roles in cancer metabolism that were secreted from E. coli in the culture media of MDA-MB-231 cells. The cells treated with the E. coli secretome showed 105 dysregulated cellular metabolites compared to controls. The dysregulated cellular metabolites were involved in the metabolism of fructose and mannose, sphingolipids, amino acids, fatty acids, amino sugar, nucleotide sugar, and pyrimidine, which are vital pathways required for the pathogenesis of BC. Our findings are the first to show that the E. coli secretome modulates the BC cells’ energy metabolism, highlighting insights into the possibility of altered metabolic events in BC tissue in the actual BC tissue microenvironment that are potentially induced by the local bacteria. Our study provides metabolic data that could be as a basis for future studies searching for the underlying mechanisms mediated by bacteria and their secretome to alter the metabolism of BC cells. MDPI 2023-02-20 /pmc/articles/PMC9964955/ /pubmed/36835626 http://dx.doi.org/10.3390/ijms24044219 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article AlMalki, Reem H. Sebaa, Rajaa Al-Ansari, Mysoon M. Al-Alwan, Monther Alwehaibi, Moudi A. Rahman, Anas M. Abdel E. coli Secretome Metabolically Modulates MDA-MB-231 Breast Cancer Cells’ Energy Metabolism |
title | E. coli Secretome Metabolically Modulates MDA-MB-231 Breast Cancer Cells’ Energy Metabolism |
title_full | E. coli Secretome Metabolically Modulates MDA-MB-231 Breast Cancer Cells’ Energy Metabolism |
title_fullStr | E. coli Secretome Metabolically Modulates MDA-MB-231 Breast Cancer Cells’ Energy Metabolism |
title_full_unstemmed | E. coli Secretome Metabolically Modulates MDA-MB-231 Breast Cancer Cells’ Energy Metabolism |
title_short | E. coli Secretome Metabolically Modulates MDA-MB-231 Breast Cancer Cells’ Energy Metabolism |
title_sort | e. coli secretome metabolically modulates mda-mb-231 breast cancer cells’ energy metabolism |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9964955/ https://www.ncbi.nlm.nih.gov/pubmed/36835626 http://dx.doi.org/10.3390/ijms24044219 |
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