Reversible regulation of metastasis by ROS-generating mtDNA mutations.
It has been controversial whether mtDNA mutations are responsible for oncogenic transformation (normal cells to develop tumors), and for malignant progression (tumor cells to develop metastases). To clarify this issue, we created trans-mitochondrial cybrids with mtDNA exchanged between mouse tumor cells that express different metastatic phenotypes. The G13997A mutation in the ND6 gene of mtDNA from high metastatic tumor cells reversibly controlled development of metastases by overproduction of reactive oxygen species (ROS), but did not control development of tumors. The mtDNA-mediated reversible control of metastasis reveals a novel function of mtDNA, and suggests that ROS scavengers may be therapeutically effective in suppressing metastasis.
Ishikawa
Kaori
K
Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan; Japan Society for the Promotion of Science (JSPS), 8 Ichiban-cho, Chiyoda-ku, Tokyo 102-8472, Japan.
Koshikawa
Nobuko
N
Takenaga
Keizo
K
Nakada
Kazuto
K
Hayashi
Jun-Ichi
J
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics / Q000502:physiology; D042967:Electron Transport Complex I / Q000235:genetics; D016166:Free Radical Scavengers / Q000494:pharmacology; D006822:Hybrid Cells; D051379:Mice; D020125:Mutation, Missense / Q000502:physiology; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015854:Up-Regulation
D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D042967:Electron Transport Complex I