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Redox regulation of EGFR steers migration of hypoxic mammary cells towards oxygen
Aerotaxis or chemotaxis to oxygen was described in bacteria 130 years ago. In eukaryotes, the main adaptation to hypoxia currently described relies on HIF transcription factors. To investigate whether aerotaxis is conserved in higher eukaryotes, an approach based on the self-generation of hypoxia af...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208388/ https://www.ncbi.nlm.nih.gov/pubmed/30382089 http://dx.doi.org/10.1038/s41467-018-06988-3 |
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author | Deygas, Mathieu Gadet, Rudy Gillet, Germain Rimokh, Ruth Gonzalo, Philippe Mikaelian, Ivan |
author_facet | Deygas, Mathieu Gadet, Rudy Gillet, Germain Rimokh, Ruth Gonzalo, Philippe Mikaelian, Ivan |
author_sort | Deygas, Mathieu |
collection | PubMed |
description | Aerotaxis or chemotaxis to oxygen was described in bacteria 130 years ago. In eukaryotes, the main adaptation to hypoxia currently described relies on HIF transcription factors. To investigate whether aerotaxis is conserved in higher eukaryotes, an approach based on the self-generation of hypoxia after cell confinement was developed. We show that epithelial cells from various tissues migrate with an extreme directionality towards oxygen to escape hypoxia, independently of the HIF pathway. We provide evidence that, concomitant to the oxygen gradient, a gradient of reactive oxygen species (ROS) develops under confinement and that antioxidants dampen aerotaxis. Finally, we establish that in mammary cells, EGF receptor, the activity of which is potentiated by ROS and inhibited by hypoxia, represents the molecular target that guides hypoxic cells to oxygen. Our results reveals that aerotaxis is a property of higher eukaryotic cells and proceeds from the conversion of oxygen into ROS. |
format | Online Article Text |
id | pubmed-6208388 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-62083882018-10-31 Redox regulation of EGFR steers migration of hypoxic mammary cells towards oxygen Deygas, Mathieu Gadet, Rudy Gillet, Germain Rimokh, Ruth Gonzalo, Philippe Mikaelian, Ivan Nat Commun Article Aerotaxis or chemotaxis to oxygen was described in bacteria 130 years ago. In eukaryotes, the main adaptation to hypoxia currently described relies on HIF transcription factors. To investigate whether aerotaxis is conserved in higher eukaryotes, an approach based on the self-generation of hypoxia after cell confinement was developed. We show that epithelial cells from various tissues migrate with an extreme directionality towards oxygen to escape hypoxia, independently of the HIF pathway. We provide evidence that, concomitant to the oxygen gradient, a gradient of reactive oxygen species (ROS) develops under confinement and that antioxidants dampen aerotaxis. Finally, we establish that in mammary cells, EGF receptor, the activity of which is potentiated by ROS and inhibited by hypoxia, represents the molecular target that guides hypoxic cells to oxygen. Our results reveals that aerotaxis is a property of higher eukaryotic cells and proceeds from the conversion of oxygen into ROS. Nature Publishing Group UK 2018-10-31 /pmc/articles/PMC6208388/ /pubmed/30382089 http://dx.doi.org/10.1038/s41467-018-06988-3 Text en © The Author(s) 2018 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 Deygas, Mathieu Gadet, Rudy Gillet, Germain Rimokh, Ruth Gonzalo, Philippe Mikaelian, Ivan Redox regulation of EGFR steers migration of hypoxic mammary cells towards oxygen |
title | Redox regulation of EGFR steers migration of hypoxic mammary cells towards oxygen |
title_full | Redox regulation of EGFR steers migration of hypoxic mammary cells towards oxygen |
title_fullStr | Redox regulation of EGFR steers migration of hypoxic mammary cells towards oxygen |
title_full_unstemmed | Redox regulation of EGFR steers migration of hypoxic mammary cells towards oxygen |
title_short | Redox regulation of EGFR steers migration of hypoxic mammary cells towards oxygen |
title_sort | redox regulation of egfr steers migration of hypoxic mammary cells towards oxygen |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208388/ https://www.ncbi.nlm.nih.gov/pubmed/30382089 http://dx.doi.org/10.1038/s41467-018-06988-3 |
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