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Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer

Maintenance of cellular pH homeostasis is fundamental to life. A number of key intracellular pH (pHi) regulating systems including the Na(+)/H(+) exchangers, the proton pump, the monocarboxylate transporters, the HCO(3)(−) transporters and exchangers and the membrane-associated and cytosolic carboni...

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Autores principales: Chiche, Johanna, Brahimi-Horn, M Christiane, Pouysségur, Jacques
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823111/
https://www.ncbi.nlm.nih.gov/pubmed/20015196
http://dx.doi.org/10.1111/j.1582-4934.2009.00994.x
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author Chiche, Johanna
Brahimi-Horn, M Christiane
Pouysségur, Jacques
author_facet Chiche, Johanna
Brahimi-Horn, M Christiane
Pouysségur, Jacques
author_sort Chiche, Johanna
collection PubMed
description Maintenance of cellular pH homeostasis is fundamental to life. A number of key intracellular pH (pHi) regulating systems including the Na(+)/H(+) exchangers, the proton pump, the monocarboxylate transporters, the HCO(3)(−) transporters and exchangers and the membrane-associated and cytosolic carbonic anhydrases cooperate in maintaining a pHi that is permissive for cell survival. A common feature of tumours is acidosis caused by hypoxia (low oxygen tension). In addition to oncogene activation and transformation, hypoxia is responsible for inducing acidosis through a shift in cellular metabolism that generates a high acid load in the tumour microenvironment. However, hypoxia and oncogene activation also allow cells to adapt to the potentially toxic effects of an excess in acidosis. Hypoxia does so by inducing the activity of a transcription factor the hypoxia-inducible factor (HIF), and particularly HIF-1, that in turn enhances the expression of a number of pHi-regulating systems that cope with acidosis. In this review, we will focus on the characterization and function of some of the hypoxia-inducible pH-regulating systems and their induction by hypoxic stress. It is essential to understand the fundamentals of pH regulation to meet the challenge consisting in targeting tumour metabolism and acidosis as an anti-tumour approach. We will summarize strategies that take advantage of intracellular and extracellular pH regulation to target the primary tumour and metastatic growth, and to turn around resistance to chemotherapy and radiotherapy.
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spelling pubmed-38231112015-04-20 Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer Chiche, Johanna Brahimi-Horn, M Christiane Pouysségur, Jacques J Cell Mol Med Reviews Maintenance of cellular pH homeostasis is fundamental to life. A number of key intracellular pH (pHi) regulating systems including the Na(+)/H(+) exchangers, the proton pump, the monocarboxylate transporters, the HCO(3)(−) transporters and exchangers and the membrane-associated and cytosolic carbonic anhydrases cooperate in maintaining a pHi that is permissive for cell survival. A common feature of tumours is acidosis caused by hypoxia (low oxygen tension). In addition to oncogene activation and transformation, hypoxia is responsible for inducing acidosis through a shift in cellular metabolism that generates a high acid load in the tumour microenvironment. However, hypoxia and oncogene activation also allow cells to adapt to the potentially toxic effects of an excess in acidosis. Hypoxia does so by inducing the activity of a transcription factor the hypoxia-inducible factor (HIF), and particularly HIF-1, that in turn enhances the expression of a number of pHi-regulating systems that cope with acidosis. In this review, we will focus on the characterization and function of some of the hypoxia-inducible pH-regulating systems and their induction by hypoxic stress. It is essential to understand the fundamentals of pH regulation to meet the challenge consisting in targeting tumour metabolism and acidosis as an anti-tumour approach. We will summarize strategies that take advantage of intracellular and extracellular pH regulation to target the primary tumour and metastatic growth, and to turn around resistance to chemotherapy and radiotherapy. Blackwell Publishing Ltd 2010-04 2009-12-08 /pmc/articles/PMC3823111/ /pubmed/20015196 http://dx.doi.org/10.1111/j.1582-4934.2009.00994.x Text en © 2009 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
spellingShingle Reviews
Chiche, Johanna
Brahimi-Horn, M Christiane
Pouysségur, Jacques
Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer
title Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer
title_full Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer
title_fullStr Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer
title_full_unstemmed Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer
title_short Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer
title_sort tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823111/
https://www.ncbi.nlm.nih.gov/pubmed/20015196
http://dx.doi.org/10.1111/j.1582-4934.2009.00994.x
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