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Untargeted Metabolomics Showed Accumulation of One-Carbon Metabolites to Facilitate DNA Methylation during Extracellular Matrix Detachment of Cancer Cells

Tumor cells detached from the extracellular matrix (ECM) undergo anoikis resistance and metabolic reprogramming to facilitate cancer cell survival and promote metastasis. During ECM detachment, cancer cells utilize genomic methylation to regulate transcriptional events. One-carbon (1C) metabolism is...

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Autores principales: Nur, Suza Mohammad, Shait Mohammed, Mohammed Razeeth, Zamzami, Mazin A., Choudhry, Hani, Ahmad, Aamir, Ateeq, Bushra, Rather, Irfan A., Khan, Mohammad Imran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951017/
https://www.ncbi.nlm.nih.gov/pubmed/35323710
http://dx.doi.org/10.3390/metabo12030267
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author Nur, Suza Mohammad
Shait Mohammed, Mohammed Razeeth
Zamzami, Mazin A.
Choudhry, Hani
Ahmad, Aamir
Ateeq, Bushra
Rather, Irfan A.
Khan, Mohammad Imran
author_facet Nur, Suza Mohammad
Shait Mohammed, Mohammed Razeeth
Zamzami, Mazin A.
Choudhry, Hani
Ahmad, Aamir
Ateeq, Bushra
Rather, Irfan A.
Khan, Mohammad Imran
author_sort Nur, Suza Mohammad
collection PubMed
description Tumor cells detached from the extracellular matrix (ECM) undergo anoikis resistance and metabolic reprogramming to facilitate cancer cell survival and promote metastasis. During ECM detachment, cancer cells utilize genomic methylation to regulate transcriptional events. One-carbon (1C) metabolism is a well-known contributor of SAM, a global substrate for methylation reactions, especially DNA methylation. DNA methylation-mediated repression of NK cell ligands MICA and MICB during ECM detachment has been overlooked. In the current work, we quantitated the impact of ECM detachment on one-carbon metabolites, expression of 1C regulatory pathway genes, and total methylation levels. Our results showed that ECM detachment promotes the accumulation of one-carbon metabolites and induces regulatory pathway genes and total DNA methylation. Furthermore, we measured the expression of well-known targets of DNA methylation in NK cell ligands in cancer cells, namely, MICA/B, during ECM detachment and observed low expression compared to ECM-attached cancer cells. Finally, we treated the ECM-detached cancer cells with vitamin C (a global methylation inhibitor) and observed a reduction in the promoter methylation of NK cell ligands, resulting in MICA/B re-expression. Treatment with vitamin C was also found to reduce global DNA methylation levels in ECM-detached cancer cells.
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spelling pubmed-89510172022-03-26 Untargeted Metabolomics Showed Accumulation of One-Carbon Metabolites to Facilitate DNA Methylation during Extracellular Matrix Detachment of Cancer Cells Nur, Suza Mohammad Shait Mohammed, Mohammed Razeeth Zamzami, Mazin A. Choudhry, Hani Ahmad, Aamir Ateeq, Bushra Rather, Irfan A. Khan, Mohammad Imran Metabolites Article Tumor cells detached from the extracellular matrix (ECM) undergo anoikis resistance and metabolic reprogramming to facilitate cancer cell survival and promote metastasis. During ECM detachment, cancer cells utilize genomic methylation to regulate transcriptional events. One-carbon (1C) metabolism is a well-known contributor of SAM, a global substrate for methylation reactions, especially DNA methylation. DNA methylation-mediated repression of NK cell ligands MICA and MICB during ECM detachment has been overlooked. In the current work, we quantitated the impact of ECM detachment on one-carbon metabolites, expression of 1C regulatory pathway genes, and total methylation levels. Our results showed that ECM detachment promotes the accumulation of one-carbon metabolites and induces regulatory pathway genes and total DNA methylation. Furthermore, we measured the expression of well-known targets of DNA methylation in NK cell ligands in cancer cells, namely, MICA/B, during ECM detachment and observed low expression compared to ECM-attached cancer cells. Finally, we treated the ECM-detached cancer cells with vitamin C (a global methylation inhibitor) and observed a reduction in the promoter methylation of NK cell ligands, resulting in MICA/B re-expression. Treatment with vitamin C was also found to reduce global DNA methylation levels in ECM-detached cancer cells. MDPI 2022-03-21 /pmc/articles/PMC8951017/ /pubmed/35323710 http://dx.doi.org/10.3390/metabo12030267 Text en © 2022 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
Nur, Suza Mohammad
Shait Mohammed, Mohammed Razeeth
Zamzami, Mazin A.
Choudhry, Hani
Ahmad, Aamir
Ateeq, Bushra
Rather, Irfan A.
Khan, Mohammad Imran
Untargeted Metabolomics Showed Accumulation of One-Carbon Metabolites to Facilitate DNA Methylation during Extracellular Matrix Detachment of Cancer Cells
title Untargeted Metabolomics Showed Accumulation of One-Carbon Metabolites to Facilitate DNA Methylation during Extracellular Matrix Detachment of Cancer Cells
title_full Untargeted Metabolomics Showed Accumulation of One-Carbon Metabolites to Facilitate DNA Methylation during Extracellular Matrix Detachment of Cancer Cells
title_fullStr Untargeted Metabolomics Showed Accumulation of One-Carbon Metabolites to Facilitate DNA Methylation during Extracellular Matrix Detachment of Cancer Cells
title_full_unstemmed Untargeted Metabolomics Showed Accumulation of One-Carbon Metabolites to Facilitate DNA Methylation during Extracellular Matrix Detachment of Cancer Cells
title_short Untargeted Metabolomics Showed Accumulation of One-Carbon Metabolites to Facilitate DNA Methylation during Extracellular Matrix Detachment of Cancer Cells
title_sort untargeted metabolomics showed accumulation of one-carbon metabolites to facilitate dna methylation during extracellular matrix detachment of cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951017/
https://www.ncbi.nlm.nih.gov/pubmed/35323710
http://dx.doi.org/10.3390/metabo12030267
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