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Antioxidants 2017, 6(4), 86;

Insights into the Dichotomous Regulation of SOD2 in Cancer

Department of Pharmacology, College of Medicine, Penn State University, Hershey, PA 17033, USA
Department of Obstetrics & Gynecology & Department of Microbiology and Immunology, College of Medicine, Penn State University, Hershey, PA 17033, USA
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208, USA
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Received: 1 October 2017 / Revised: 24 October 2017 / Accepted: 1 November 2017 / Published: 3 November 2017
(This article belongs to the Special Issue Superoxide Dismutase (SOD) Enzymes, Mimetics and Oxygen Radicals)
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While loss of antioxidant expression and the resultant oxidant-dependent damage to cellular macromolecules is key to tumorigenesis, it has become evident that effective oxidant scavenging is conversely necessary for successful metastatic spread. This dichotomous role of antioxidant enzymes in cancer highlights their context-dependent regulation during different stages of tumor development. A prominent example of an antioxidant enzyme with such a dichotomous role and regulation is the mitochondria-localized manganese superoxide dismutase SOD2 (MnSOD). SOD2 has both tumor suppressive and promoting functions, which are primarily related to its role as a mitochondrial superoxide scavenger and H2O2 regulator. However, unlike true tumor suppressor- or onco-genes, the SOD2 gene is not frequently lost, or rarely mutated or amplified in cancer. This allows SOD2 to be either repressed or activated contingent on context-dependent stimuli, leading to its dichotomous function in cancer. Here, we describe some of the mechanisms that underlie SOD2 regulation in tumor cells. While much is known about the transcriptional regulation of the SOD2 gene, including downregulation by epigenetics and activation by stress response transcription factors, further research is required to understand the post-translational modifications that regulate SOD2 activity in cancer cells. Moreover, future work examining the spatio-temporal nature of SOD2 regulation in the context of changing tumor microenvironments is necessary to allows us to better design oxidant- or antioxidant-based therapeutic strategies that target the adaptable antioxidant repertoire of tumor cells. View Full-Text
Keywords: superoxide dismutase; SOD2; MnSOD; SOD2 regulation; cancer superoxide dismutase; SOD2; MnSOD; SOD2 regulation; cancer

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Kim, Y.S.; Gupta Vallur, P.; Phaëton, R.; Mythreye, K.; Hempel, N. Insights into the Dichotomous Regulation of SOD2 in Cancer. Antioxidants 2017, 6, 86.

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