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The impact of oncogenic RAS on redox balance and implications for cancer development

The RAS family of proto-oncogenes comprises HRAS, KRAS, and NRAS, which are among the most mutated genes in human cancers. The RAS family genes encode small GTPases that coordinate key signaling pathways in response to growth factors. Mutations in RAS result in a constitutively active form of the pr...

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Autores principales: Lim, Jonathan K. M., Leprivier, Gabriel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920345/
https://www.ncbi.nlm.nih.gov/pubmed/31852884
http://dx.doi.org/10.1038/s41419-019-2192-y
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author Lim, Jonathan K. M.
Leprivier, Gabriel
author_facet Lim, Jonathan K. M.
Leprivier, Gabriel
author_sort Lim, Jonathan K. M.
collection PubMed
description The RAS family of proto-oncogenes comprises HRAS, KRAS, and NRAS, which are among the most mutated genes in human cancers. The RAS family genes encode small GTPases that coordinate key signaling pathways in response to growth factors. Mutations in RAS result in a constitutively active form of the protein that supports cellular transformation and tumorigenesis. The mechanisms of oncogenic RAS-mediated transformation encompass uncontrolled proliferation and inhibition of cell death through overactivation of the RAF-MEK-ERK and the PI3K-AKT pathways, respectively. In addition, the control of redox balance by RAS has also been proposed to play a role in its oncogenic properties. However, the exact role of redox balance in mediating mutant RAS transformation is still under debate. Here, we present, on one hand, the involvement of pro-oxidant components in oncogenic RAS transformation, such as NADPH oxidases and mitochondrial reactive oxygen species, and how these promote transformation. On the other hand, we describe the contribution of antioxidant components to mutant RAS transformation, including Nrf2, glutathione biosynthesis and xCT, as well as the mechanisms by which antioxidant programs drive transformation. Finally, we aim to reconcile the seemingly opposite effects of oncogenic RAS on redox balance and discuss a model for the complementary role of both pro-oxidant and antioxidant pathways in mutant RAS-driven tumor progression.
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spelling pubmed-69203452019-12-20 The impact of oncogenic RAS on redox balance and implications for cancer development Lim, Jonathan K. M. Leprivier, Gabriel Cell Death Dis Review Article The RAS family of proto-oncogenes comprises HRAS, KRAS, and NRAS, which are among the most mutated genes in human cancers. The RAS family genes encode small GTPases that coordinate key signaling pathways in response to growth factors. Mutations in RAS result in a constitutively active form of the protein that supports cellular transformation and tumorigenesis. The mechanisms of oncogenic RAS-mediated transformation encompass uncontrolled proliferation and inhibition of cell death through overactivation of the RAF-MEK-ERK and the PI3K-AKT pathways, respectively. In addition, the control of redox balance by RAS has also been proposed to play a role in its oncogenic properties. However, the exact role of redox balance in mediating mutant RAS transformation is still under debate. Here, we present, on one hand, the involvement of pro-oxidant components in oncogenic RAS transformation, such as NADPH oxidases and mitochondrial reactive oxygen species, and how these promote transformation. On the other hand, we describe the contribution of antioxidant components to mutant RAS transformation, including Nrf2, glutathione biosynthesis and xCT, as well as the mechanisms by which antioxidant programs drive transformation. Finally, we aim to reconcile the seemingly opposite effects of oncogenic RAS on redox balance and discuss a model for the complementary role of both pro-oxidant and antioxidant pathways in mutant RAS-driven tumor progression. Nature Publishing Group UK 2019-12-18 /pmc/articles/PMC6920345/ /pubmed/31852884 http://dx.doi.org/10.1038/s41419-019-2192-y 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 Review Article
Lim, Jonathan K. M.
Leprivier, Gabriel
The impact of oncogenic RAS on redox balance and implications for cancer development
title The impact of oncogenic RAS on redox balance and implications for cancer development
title_full The impact of oncogenic RAS on redox balance and implications for cancer development
title_fullStr The impact of oncogenic RAS on redox balance and implications for cancer development
title_full_unstemmed The impact of oncogenic RAS on redox balance and implications for cancer development
title_short The impact of oncogenic RAS on redox balance and implications for cancer development
title_sort impact of oncogenic ras on redox balance and implications for cancer development
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920345/
https://www.ncbi.nlm.nih.gov/pubmed/31852884
http://dx.doi.org/10.1038/s41419-019-2192-y
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