Mitochondrial superoxide dismutase 2 mediates γ-irradiation-induced cancer cell invasion.

Abstract

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-XL. Given that Bcl-XL can increase O2•- 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 O2•- to hydrogen peroxide (H2O2). In contrast to O2•-, H2O2 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-XL, 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.

• Authors: Chan-Hun Jung, Eun Mi Kim, Jie-Young Song, Jong Kuk Park, Hong-Duck Um
• Journal: Experimental & molecular medicine (Exp Mol Med) Vol. 51 Issue 2 Pg. 1-10 (02 12 2019) ISSN: 2092-6413 [Electronic] United States
• PMID: 30755594 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Interleukin-6
• Reactive Oxygen Species
• STAT3 Transcription Factor
• Superoxide Dismutase
• superoxide dismutase 2
• src-Family Kinases

Topics

• Biomarkers
• Cell Line, Tumor
• Cell Movement (genetics)
• Gamma Rays
• Gene Expression
• Humans
• Interleukin-6 (metabolism)
• Mitochondria (genetics, metabolism, radiation effects)
• Oxidative Stress
• Phosphorylation
• Radiation Tolerance (genetics)
• Reactive Oxygen Species (metabolism)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (drug effects)
• Superoxide Dismutase (genetics, metabolism)
• src-Family Kinases (genetics, metabolism)