The Entanglement between Mitochondrial DNA and Tumor Metastasis

SIMPLE SUMMARY: Mitochondrial dysfunction is one of the main features of cancer cells. As genetic material in mitochondria, mitochondrial DNA (mtDNA) variations and dysregulation of mitochondria-encoded genes have been shown to correlate with survival outcomes in cancer patients. Cancer metastasis is often a major cause of treatment failure, which is a multi-step cascade process. With the development of gene sequencing and in vivo modeling technology, the role of mtDNA in cancer metastasis has been continuously explored. Our review systematically provides a summary of the multiple roles of mtDNA in cancer metastasis and presents the broad prospects for mtDNA in cancer prediction and therapy. ABSTRACT: Mitochondrial DNA, the genetic material in mitochondria, encodes essential oxidative phosphorylation proteins and plays an important role in mitochondrial respiration and energy transfer. With the development of genome sequencing and the emergence of novel in vivo modeling techniques, the role of mtDNA in cancer biology is gaining more attention. Abnormalities of mtDNA result in not only mitochondrial dysfunction of the the cancer cells and malignant behaviors, but regulation of the tumor microenvironment, which becomes more aggressive. Here, we review the recent progress in the regulation of cancer metastasis using mtDNA and the underlying mechanisms, which may identify opportunities for finding novel cancer prediction and therapeutic targets.