Cancer and Metastasis Reviews

, Volume 37, Issue 4, pp 615–632 | Cite as

Roles of the mitochondrial genetics in cancer metastasis: not to be ignored any longer

  • Thomas C. Beadnell
  • Adam D. Scheid
  • Carolyn J. Vivian
  • Danny R. WelchEmail author


Mitochondrial DNA (mtDNA) encodes for only a fraction of the proteins that are encoded within the nucleus, and therefore has typically been regarded as a lesser player in cancer biology and metastasis. Accumulating evidence, however, supports an increased role for mtDNA impacting tumor progression and metastatic susceptibility. Unfortunately, due to this delay, there is a dearth of data defining the relative contributions of specific mtDNA polymorphisms (SNP), which leads to an inability to effectively use these polymorphisms to guide and enhance therapeutic strategies and diagnosis. In addition, evidence also suggests that differences in mtDNA impact not only the cancer cells but also the cells within the surrounding tumor microenvironment, suggesting a broad encompassing role for mtDNA polymorphisms in regulating the disease progression. mtDNA may have profound implications in the regulation of cancer biology and metastasis. However, there are still great lengths to go to understand fully its contributions. Thus, herein, we discuss the recent advances in our understanding of mtDNA in cancer and metastasis, providing a framework for future functional validation and discovery.


Mitochondrial genetics Polymorphism Metastasis Metabolism Tumor progression 



Base pair


Cancer-associated fibroblasts


Cell-free DNA


Circulating tumor cell


Reactive oxygen species


Electron transport chain


Epigenome-wide association study


Epithelial-mesenchymal transition


Extracellular acidification ratio


Genome-wide association study


Mitochondrial DNA


Mitochondrial-nuclear exchange mouse


Next-generation sequencing


Nuclear DNA




oxygen consumption ratio


Single-nucleotide polymorphism



We are deeply indebted to all members of the Welch lab, Isidore Rigoutsos and Kent Hunter for insights and inspiration. We apologize to any authors whose work was omitted due to article guidelines.

Funding information

Work done in the authors’ labs was funded by Susan G. Komen for the Cure (SAC110037) and the National Foundation for Cancer Research. Additional funding support was provided by the U.S. Army Medical Research Defense Command Breast Cancer Research Program under Award No. W81XWH1810450, (TCB); National Cancer Institute P30-CA168524 (DRW), and National Institutes of Health GM103418 (TCB and DRW). Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Thomas C. Beadnell
    • 1
  • Adam D. Scheid
    • 1
  • Carolyn J. Vivian
    • 1
  • Danny R. Welch
    • 1
    • 2
    Email author
  1. 1.Department of Cancer BiologyThe Kansas University Medical CenterKansas CityUSA
  2. 2.The University of Kansas Cancer CenterKansas CityUSA

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