ROS-Generating Mitochondrial DNA Mutations Can Regulate Tumor Cell Metastasis
By Kaori Ishikawa, K. Takenaga, Miho Akimoto, N. Koshikawa, Ayako Yamaguchi, Hirotake Imanishi, K. Nakada, Y. Honma, J. Hayashi. Science, 2008
1,366 citations recorded by the source corpus.
Mutations in mitochondrial DNA (mtDNA) occur at high frequency in human tumors, but whether these mutations alter tumor cell behavior has been unclear. We used cytoplasmic hybrid (cybrid) technology to replace the endogenous mtDNA in a mouse tumor cell line that was poorly metastatic with mtDNA from a cell line that was highly metastatic, and vice versa. Using assays of metastasis in mice, we found that the recipient tumor cells acquired the metastatic potential of the transferred mtDNA. The mtDNA conferring high metastatic potential contained G13997A and 13885insC mutations in the gene encoding NADH (reduced form of nicotinamide adenine dinucleotide) dehydrogenase subunit 6 (ND6). These mutations produced a deficiency in respiratory complex I activity and were associated with overproduction of reactive oxygen species (ROS). Pretreatment of the highly metastatic tumor cells with ROS scavengers suppressed their metastatic potential in mice. These results indicate that mtDNA mutations can contribute to tumor progression by enhancing the metastatic potential of tumor cells.
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/1487cd41863ca507224f9cf99660d94735630933
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In Cancer Research
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- J. Pouysségur
- David M. Sabatini
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In Molecular Biology
- Guido Kroemer
- L. Galluzzi
- Navdeep S. Chandel
- C. V. Dang
- David M. Sabatini
- J. Pouysségur
- Ralph J. Deberardinis
- Lucas B. Sullivan
Citations in the corpus
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- Otto Warburg's contributions to current concepts of cancer metabolism (2011, background): “Furthermore, an MT-ND6 mutation introduced by cybrid technology into a mouse tumour cell line is associated with overproduction of oxyradicals and tumour cell metastasis; pretreatment of the tumours with oxyradical scavengers suppressed metastasis, suggesting that alterations of redox balance by m”