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Another Consequence of the Warburg Effect? Metabolic Regulation of Na(+)/H(+) Exchangers May Link Aerobic Glycolysis to Cell Growth
To adjust cell growth and proliferation to changing environmental conditions or developmental requirements, cells have evolved a remarkable network of signaling cascades that integrates cues from cellular metabolism, growth factor availability and a large variety of stresses. In these networks, cell...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462004/ https://www.ncbi.nlm.nih.gov/pubmed/32974190 http://dx.doi.org/10.3389/fonc.2020.01561 |
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author | Birkeland, Eivind Salmorin Koch, Lisa Maria Dechant, Reinhard |
author_facet | Birkeland, Eivind Salmorin Koch, Lisa Maria Dechant, Reinhard |
author_sort | Birkeland, Eivind Salmorin |
collection | PubMed |
description | To adjust cell growth and proliferation to changing environmental conditions or developmental requirements, cells have evolved a remarkable network of signaling cascades that integrates cues from cellular metabolism, growth factor availability and a large variety of stresses. In these networks, cellular information flow is mostly mediated by posttranslational modifications, most notably phosphorylation, or signaling molecules such as GTPases. Yet, a large body of evidence also implicates cytosolic pH (pHc) as a highly conserved cellular signal driving cell growth and proliferation, suggesting that pH-dependent protonation of specific proteins also regulates cellular signaling. In mammalian cells, pHc is regulated by growth factor derived signals and responds to metabolic cues in response to glucose stimulation. Importantly, high pHc has also been identified as a hall mark of cancer, but mechanisms of pH regulation in cancer are only poorly understood. Here, we discuss potential mechanisms of pH regulation with emphasis on metabolic signals regulating pHc by Na(+)/H(+)-exchangers. We hypothesize that elevated NHE activity and pHc in cancer are a direct consequence of the metabolic adaptations in tumor cells including enhanced aerobic glycolysis, generally referred to as the Warburg effect. This hypothesis not only provides an explanation for the growth advantage conferred by a switch to aerobic glycolysis beyond providing precursors for accumulation of biomass, but also suggests that treatments targeting pH regulation as a potential anti-cancer therapy may effectively target the result of altered tumor cell metabolism. |
format | Online Article Text |
id | pubmed-7462004 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74620042020-09-23 Another Consequence of the Warburg Effect? Metabolic Regulation of Na(+)/H(+) Exchangers May Link Aerobic Glycolysis to Cell Growth Birkeland, Eivind Salmorin Koch, Lisa Maria Dechant, Reinhard Front Oncol Oncology To adjust cell growth and proliferation to changing environmental conditions or developmental requirements, cells have evolved a remarkable network of signaling cascades that integrates cues from cellular metabolism, growth factor availability and a large variety of stresses. In these networks, cellular information flow is mostly mediated by posttranslational modifications, most notably phosphorylation, or signaling molecules such as GTPases. Yet, a large body of evidence also implicates cytosolic pH (pHc) as a highly conserved cellular signal driving cell growth and proliferation, suggesting that pH-dependent protonation of specific proteins also regulates cellular signaling. In mammalian cells, pHc is regulated by growth factor derived signals and responds to metabolic cues in response to glucose stimulation. Importantly, high pHc has also been identified as a hall mark of cancer, but mechanisms of pH regulation in cancer are only poorly understood. Here, we discuss potential mechanisms of pH regulation with emphasis on metabolic signals regulating pHc by Na(+)/H(+)-exchangers. We hypothesize that elevated NHE activity and pHc in cancer are a direct consequence of the metabolic adaptations in tumor cells including enhanced aerobic glycolysis, generally referred to as the Warburg effect. This hypothesis not only provides an explanation for the growth advantage conferred by a switch to aerobic glycolysis beyond providing precursors for accumulation of biomass, but also suggests that treatments targeting pH regulation as a potential anti-cancer therapy may effectively target the result of altered tumor cell metabolism. Frontiers Media S.A. 2020-08-18 /pmc/articles/PMC7462004/ /pubmed/32974190 http://dx.doi.org/10.3389/fonc.2020.01561 Text en Copyright © 2020 Birkeland, Koch and Dechant. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Birkeland, Eivind Salmorin Koch, Lisa Maria Dechant, Reinhard Another Consequence of the Warburg Effect? Metabolic Regulation of Na(+)/H(+) Exchangers May Link Aerobic Glycolysis to Cell Growth |
title | Another Consequence of the Warburg Effect? Metabolic Regulation of Na(+)/H(+) Exchangers May Link Aerobic Glycolysis to Cell Growth |
title_full | Another Consequence of the Warburg Effect? Metabolic Regulation of Na(+)/H(+) Exchangers May Link Aerobic Glycolysis to Cell Growth |
title_fullStr | Another Consequence of the Warburg Effect? Metabolic Regulation of Na(+)/H(+) Exchangers May Link Aerobic Glycolysis to Cell Growth |
title_full_unstemmed | Another Consequence of the Warburg Effect? Metabolic Regulation of Na(+)/H(+) Exchangers May Link Aerobic Glycolysis to Cell Growth |
title_short | Another Consequence of the Warburg Effect? Metabolic Regulation of Na(+)/H(+) Exchangers May Link Aerobic Glycolysis to Cell Growth |
title_sort | another consequence of the warburg effect? metabolic regulation of na(+)/h(+) exchangers may link aerobic glycolysis to cell growth |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462004/ https://www.ncbi.nlm.nih.gov/pubmed/32974190 http://dx.doi.org/10.3389/fonc.2020.01561 |
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