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Computational modeling to determine key regulators of hypoxia effects on the lactate production in the glycolysis pathway
In solid tumors, hypoxia can trigger aberrant expression of transcription factors and genes, resulting in abnormal biological functions such as altered energetic pathways in cancer cells. Glucose metabolism is an important part of this phenomenon, which is associated with changes in the functional e...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280308/ https://www.ncbi.nlm.nih.gov/pubmed/32514127 http://dx.doi.org/10.1038/s41598-020-66059-w |
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author | Hashemzadeh, Shabnam Shahmorad, Sedaghat Rafii-Tabar, Hashem Omidi, Yadollah |
author_facet | Hashemzadeh, Shabnam Shahmorad, Sedaghat Rafii-Tabar, Hashem Omidi, Yadollah |
author_sort | Hashemzadeh, Shabnam |
collection | PubMed |
description | In solid tumors, hypoxia can trigger aberrant expression of transcription factors and genes, resulting in abnormal biological functions such as altered energetic pathways in cancer cells. Glucose metabolism is an important part of this phenomenon, which is associated with changes in the functional expression of transporters and enzymes involved in the glycolysis pathway. The latter phenomenon can finally lead to the lactate accumulation and pH dysregulation in the tumor microenvironment and subsequently further invasion and metastasis of cancer cells. Having capitalized on the computational modeling, in this study, for the first time, we aimed to investigate the effects of hypoxia-induced factor-1 (HIF-1) mediated hypoxia on the magnitude of functional expression of all the enzymes and transporters involved in the glycolysis process. The main objective was to establish a quantitative relationship between the hypoxia intensity and the intracellular lactate levels and determine the key regulators of the glycolysis pathway. This model clearly showed an increase in the lactate concentration during the oxygen depletion. The proposed model also predicted that the phosphofructokinase-1 and phosphoglucomutase enzymes might play the most important roles in the regulation of the lactate production. |
format | Online Article Text |
id | pubmed-7280308 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-72803082020-06-15 Computational modeling to determine key regulators of hypoxia effects on the lactate production in the glycolysis pathway Hashemzadeh, Shabnam Shahmorad, Sedaghat Rafii-Tabar, Hashem Omidi, Yadollah Sci Rep Article In solid tumors, hypoxia can trigger aberrant expression of transcription factors and genes, resulting in abnormal biological functions such as altered energetic pathways in cancer cells. Glucose metabolism is an important part of this phenomenon, which is associated with changes in the functional expression of transporters and enzymes involved in the glycolysis pathway. The latter phenomenon can finally lead to the lactate accumulation and pH dysregulation in the tumor microenvironment and subsequently further invasion and metastasis of cancer cells. Having capitalized on the computational modeling, in this study, for the first time, we aimed to investigate the effects of hypoxia-induced factor-1 (HIF-1) mediated hypoxia on the magnitude of functional expression of all the enzymes and transporters involved in the glycolysis process. The main objective was to establish a quantitative relationship between the hypoxia intensity and the intracellular lactate levels and determine the key regulators of the glycolysis pathway. This model clearly showed an increase in the lactate concentration during the oxygen depletion. The proposed model also predicted that the phosphofructokinase-1 and phosphoglucomutase enzymes might play the most important roles in the regulation of the lactate production. Nature Publishing Group UK 2020-06-08 /pmc/articles/PMC7280308/ /pubmed/32514127 http://dx.doi.org/10.1038/s41598-020-66059-w Text en © The Author(s) 2020 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 Hashemzadeh, Shabnam Shahmorad, Sedaghat Rafii-Tabar, Hashem Omidi, Yadollah Computational modeling to determine key regulators of hypoxia effects on the lactate production in the glycolysis pathway |
title | Computational modeling to determine key regulators of hypoxia effects on the lactate production in the glycolysis pathway |
title_full | Computational modeling to determine key regulators of hypoxia effects on the lactate production in the glycolysis pathway |
title_fullStr | Computational modeling to determine key regulators of hypoxia effects on the lactate production in the glycolysis pathway |
title_full_unstemmed | Computational modeling to determine key regulators of hypoxia effects on the lactate production in the glycolysis pathway |
title_short | Computational modeling to determine key regulators of hypoxia effects on the lactate production in the glycolysis pathway |
title_sort | computational modeling to determine key regulators of hypoxia effects on the lactate production in the glycolysis pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280308/ https://www.ncbi.nlm.nih.gov/pubmed/32514127 http://dx.doi.org/10.1038/s41598-020-66059-w |
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