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Mitochondrial superoxide dismutase 2 mediates γ-irradiation-induced cancer cell invasion
Sublethal doses of γ-rays promote cancer cell invasion by stimulating a signaling pathway that sequentially involves p53, sulfatase 2 (SULF2), β-catenin, interleukin-6 (IL-6), signal transducer and activator of transcription 3 (STAT3), and Bcl-X(L). Given that Bcl-X(L) can increase O(2)(•−) producti...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372678/ https://www.ncbi.nlm.nih.gov/pubmed/30755594 http://dx.doi.org/10.1038/s12276-019-0207-5 |
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author | Jung, Chan-Hun Kim, Eun Mi Song, Jie-Young Park, Jong Kuk Um, Hong-Duck |
author_facet | Jung, Chan-Hun Kim, Eun Mi Song, Jie-Young Park, Jong Kuk Um, Hong-Duck |
author_sort | Jung, Chan-Hun |
collection | PubMed |
description | Sublethal doses of γ-rays promote cancer cell invasion by stimulating a signaling pathway that sequentially involves p53, sulfatase 2 (SULF2), β-catenin, interleukin-6 (IL-6), signal transducer and activator of transcription 3 (STAT3), and Bcl-X(L). Given that Bcl-X(L) can increase O(2)(•−) production by stimulating respiratory complex I, the possible role of mitochondrial reactive oxygen species (ROS) in γ-irradiation-induced cell invasion was investigated. Indeed, γ-irradiation promoted cell invasion by increasing mitochondrial ROS levels, which was prevented by metformin, an inhibitor of complex I. γ-Irradiation-stimulated STAT3 increased the expression of superoxide dismutase 2 (SOD2), a mitochondrial enzyme that catalyzes the conversion of O(2)(•−) to hydrogen peroxide (H(2)O(2)). In contrast to O(2)(•−), H(2)O(2) functions as a signaling molecule. γ-Irradiation consistently stimulated the Src-dependent invasion pathway in a manner dependent on both complex I and SOD2. SOD2 was also essential for the invasion of un-irradiated cancer cells induced by upregulation of Bcl-X(L), an intracellular oncogene, or extracellular factors, such as SULF2 and IL-6. Overall, these data suggested that SOD2 is critical for the malignant effects of radiotherapy and tumor progression through diverse endogenous factors. |
format | Online Article Text |
id | pubmed-6372678 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63726782019-02-25 Mitochondrial superoxide dismutase 2 mediates γ-irradiation-induced cancer cell invasion Jung, Chan-Hun Kim, Eun Mi Song, Jie-Young Park, Jong Kuk Um, Hong-Duck Exp Mol Med Article Sublethal doses of γ-rays promote cancer cell invasion by stimulating a signaling pathway that sequentially involves p53, sulfatase 2 (SULF2), β-catenin, interleukin-6 (IL-6), signal transducer and activator of transcription 3 (STAT3), and Bcl-X(L). Given that Bcl-X(L) can increase O(2)(•−) production by stimulating respiratory complex I, the possible role of mitochondrial reactive oxygen species (ROS) in γ-irradiation-induced cell invasion was investigated. Indeed, γ-irradiation promoted cell invasion by increasing mitochondrial ROS levels, which was prevented by metformin, an inhibitor of complex I. γ-Irradiation-stimulated STAT3 increased the expression of superoxide dismutase 2 (SOD2), a mitochondrial enzyme that catalyzes the conversion of O(2)(•−) to hydrogen peroxide (H(2)O(2)). In contrast to O(2)(•−), H(2)O(2) functions as a signaling molecule. γ-Irradiation consistently stimulated the Src-dependent invasion pathway in a manner dependent on both complex I and SOD2. SOD2 was also essential for the invasion of un-irradiated cancer cells induced by upregulation of Bcl-X(L), an intracellular oncogene, or extracellular factors, such as SULF2 and IL-6. Overall, these data suggested that SOD2 is critical for the malignant effects of radiotherapy and tumor progression through diverse endogenous factors. Nature Publishing Group UK 2019-02-12 /pmc/articles/PMC6372678/ /pubmed/30755594 http://dx.doi.org/10.1038/s12276-019-0207-5 Text en © The Author(s) 2019 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 Jung, Chan-Hun Kim, Eun Mi Song, Jie-Young Park, Jong Kuk Um, Hong-Duck Mitochondrial superoxide dismutase 2 mediates γ-irradiation-induced cancer cell invasion |
title | Mitochondrial superoxide dismutase 2 mediates γ-irradiation-induced cancer cell invasion |
title_full | Mitochondrial superoxide dismutase 2 mediates γ-irradiation-induced cancer cell invasion |
title_fullStr | Mitochondrial superoxide dismutase 2 mediates γ-irradiation-induced cancer cell invasion |
title_full_unstemmed | Mitochondrial superoxide dismutase 2 mediates γ-irradiation-induced cancer cell invasion |
title_short | Mitochondrial superoxide dismutase 2 mediates γ-irradiation-induced cancer cell invasion |
title_sort | mitochondrial superoxide dismutase 2 mediates γ-irradiation-induced cancer cell invasion |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372678/ https://www.ncbi.nlm.nih.gov/pubmed/30755594 http://dx.doi.org/10.1038/s12276-019-0207-5 |
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