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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...

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Autores principales: Jung, Chan-Hun, Kim, Eun Mi, Song, Jie-Young, Park, Jong Kuk, Um, Hong-Duck
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
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.
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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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