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Longitudinal dynamics of the tumor hypoxia response: From enzyme activity to biological phenotype

Poor oxygenation (hypoxia) is a common spatially heterogeneous feature of human tumors. Biological responses to tumor hypoxia are orchestrated by the decreased activity of oxygen-dependent enzymes. The affinity of these enzymes for oxygen positions them along a continuum of oxygen sensing that defin...

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Autores principales: Lee, Sandy Che-Eun S., Pyo, Andrea Hye An, Koritzinsky, Marianne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10664991/
https://www.ncbi.nlm.nih.gov/pubmed/37992163
http://dx.doi.org/10.1126/sciadv.adj6409
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author Lee, Sandy Che-Eun S.
Pyo, Andrea Hye An
Koritzinsky, Marianne
author_facet Lee, Sandy Che-Eun S.
Pyo, Andrea Hye An
Koritzinsky, Marianne
author_sort Lee, Sandy Che-Eun S.
collection PubMed
description Poor oxygenation (hypoxia) is a common spatially heterogeneous feature of human tumors. Biological responses to tumor hypoxia are orchestrated by the decreased activity of oxygen-dependent enzymes. The affinity of these enzymes for oxygen positions them along a continuum of oxygen sensing that defines their roles in launching reactive and adaptive cellular responses. These responses encompass regulation of all steps in the central dogma, with rapid perturbation of the metabolome and proteome followed by more persistent reprogramming of the transcriptome and epigenome. Core hypoxia response genes and pathways are commonly regulated at multiple inflection points, fine-tuning the dependencies on oxygen concentration and hypoxia duration. Ultimately, shifts in the activity of oxygen-sensing enzymes directly or indirectly endow cells with intrinsic hypoxia tolerance and drive processes that are associated with aggressive phenotypes in cancer including angiogenesis, migration, invasion, immune evasion, epithelial mesenchymal transition, and stemness.
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spelling pubmed-106649912023-11-22 Longitudinal dynamics of the tumor hypoxia response: From enzyme activity to biological phenotype Lee, Sandy Che-Eun S. Pyo, Andrea Hye An Koritzinsky, Marianne Sci Adv Biomedicine and Life Sciences Poor oxygenation (hypoxia) is a common spatially heterogeneous feature of human tumors. Biological responses to tumor hypoxia are orchestrated by the decreased activity of oxygen-dependent enzymes. The affinity of these enzymes for oxygen positions them along a continuum of oxygen sensing that defines their roles in launching reactive and adaptive cellular responses. These responses encompass regulation of all steps in the central dogma, with rapid perturbation of the metabolome and proteome followed by more persistent reprogramming of the transcriptome and epigenome. Core hypoxia response genes and pathways are commonly regulated at multiple inflection points, fine-tuning the dependencies on oxygen concentration and hypoxia duration. Ultimately, shifts in the activity of oxygen-sensing enzymes directly or indirectly endow cells with intrinsic hypoxia tolerance and drive processes that are associated with aggressive phenotypes in cancer including angiogenesis, migration, invasion, immune evasion, epithelial mesenchymal transition, and stemness. American Association for the Advancement of Science 2023-11-22 /pmc/articles/PMC10664991/ /pubmed/37992163 http://dx.doi.org/10.1126/sciadv.adj6409 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Lee, Sandy Che-Eun S.
Pyo, Andrea Hye An
Koritzinsky, Marianne
Longitudinal dynamics of the tumor hypoxia response: From enzyme activity to biological phenotype
title Longitudinal dynamics of the tumor hypoxia response: From enzyme activity to biological phenotype
title_full Longitudinal dynamics of the tumor hypoxia response: From enzyme activity to biological phenotype
title_fullStr Longitudinal dynamics of the tumor hypoxia response: From enzyme activity to biological phenotype
title_full_unstemmed Longitudinal dynamics of the tumor hypoxia response: From enzyme activity to biological phenotype
title_short Longitudinal dynamics of the tumor hypoxia response: From enzyme activity to biological phenotype
title_sort longitudinal dynamics of the tumor hypoxia response: from enzyme activity to biological phenotype
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10664991/
https://www.ncbi.nlm.nih.gov/pubmed/37992163
http://dx.doi.org/10.1126/sciadv.adj6409
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