Amazing Roles of The Mitochondrial DNA in Cancer Metastasis
Amazing Roles of The Mitochondrial DNA in Cancer Metastasis
Samaneh Dalali,1,*Fatemeh Kaviani,2
1. Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran 2. Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
Introduction: Tumor metastasis is a series of invasive and metastatic cascades in which tumor cells detonate from the original tumor to reach surrounding or distal tissues to form new lesions. It is the result of the interaction between tumor cells and the tumor microenvironment. Metastasis is the main cause of death in tumor patients, with most patients dying from the spread of the cancer rather than the primary tumor.
Mitochondrial DNA, the genetic material in mitochondria, encodes essential oxidative phosphorylation proteins and plays an important role in mitochondrial respiration and energy transfer. This genetic material has a circular structure and 37 genes. Maternally inherited mitochondrial DNA (mtDNA) is thought to contribute to cancer development and prognosis.
mtDNA is an important factor in tumor initiation and progression. As more in-depth studies of mitochondrial-encoded factors emerge, this may lead to exciting advances in targeting mtDNA to inhibit tumor metastasis. This review summarizes the structure and function of the mitochondrial genome and the relationship between mtDNA and tumor metastasis. Our goal is to establish a framework in related fields and address the role of the mitochondrial genome in tumor metastasis.
Methods: The researchers used a new mouse model, a model of mitochondrial nuclear exchange called MNX, to investigate whether the mitochondrial genome influences tumor incubation and metastasis efficiency. In another study, Using cytoplasmic hybrid (cybrid) technology, Ishikawa et al. replaced the endogenous mtDNA of a poorly metastatic mouse tumor cell line with mtDNA of a highly metastatic mouse tumor cell line, and found that the recipient tumor cells acquired the metastatic potential of the transferred mtDNA.
Results: Studies have supposed that replacing mtDNA from poorly metastatic tumor cells with mtDNA from highly metastatic tumor cells in mice via cytoplasmic hybrid (cybrid) technology could result in better metastatic capacity. Thus, mtDNA alterations have an important role in enhancing a tumor’s metastatic capacity. mtDNA mutations (m.13997G>A, p.P25L and 13885insC in the ND6) can enhance the metastatic potential of tumor cells by inducing complex I defects resulting in increased ROS production. These results indicate that mtDNA mutations can contribute to tumor progression by enhancing the metastatic potential of tumor cells. mtDNA mutations can also enhance cancer metastasis by promoting apoptotic resistance in cancer cells via activating the PI3K/Akt signaling pathway.
Conclusion: If we can summarize the characteristics of mtDNA mutation between tumorigenesis and metastasis, this may provide a great direction for the early diagnosis of cancer and the prediction of tumor aggressiveness. To date, there is no clear evidence of a definitive relationship between mtDNA and tumor metastasis, but some non-random changes in the mitochondrial genome associated with tumor progression have been reported in many tumor types.