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Mitochondrial dysfunction and cancer metastasis

  • MINI-REVIEW
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Journal of Bioenergetics and Biomembranes Aims and scope Submit manuscript

Abstract

Mitochondria have an essential role in powering cells by generating ATP following the metabolism of pyruvate derived from glycolysis. They are also the major source of generating reactive oxygen species (ROS), which have regulatory roles in cell death and proliferation. Mutations in mitochondrial DNA (mtDNA) and dysregulation of mitochondrial metabolism have been frequently described in human tumors. Although the role of oxidative stress as the consequence of mtDNA mutations and/or altered mitochondrial functions has been demonstrated in carciongenesis, a causative role of mitochondria in tumor progression has only been demonstrated recently. Specifically, the subject of this mini-review focuses on the role of mitochondria in promoting cancer metastasis. Cancer relapse and the subsequent spreading of cancer cells to distal sites are leading causes of morbidity and mortality in cancer patients. Despite its clinical importance, the underlying mechanisms of metastasis remain to be elucidated. Recently, it was demonstrated that mitochondrial oxidative stress could actively promote tumor progression and increase the metastatic potential of cancer cells. The purpose of this mini-review is to summarize current investigations of the roles of mitochondria in cancer metastasis. Future development of diagnostic and therapeutic strategies for patients with advanced cancer will benefit from the new knowledge of mitochondrial metabolism in epithelial cancer cells and the tumor stroma.

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References

  • Brandon, M., Baldi, P. and Wallace, D.C. (2006). Mitochondrial mutations in cancer. Oncogene 25, 4647-62

    Article  CAS  Google Scholar 

  • Chen, E.I. et al. (2007). Adaptation of energy metabolism in breast cancer brain metastases. Cancer Res 67, 1472-86

    Article  CAS  Google Scholar 

  • Chen, X., Li, J., Hou, J., Xie, Z. and Yang, F. (2010). Mammalian mitochondrial proteomics: insights into mitochondrial functions and mitochondria-related diseases. Expert Rev Proteomics 7, 333-45

    Article  CAS  Google Scholar 

  • Desouki, M.M., Kulawiec, M., Bansal, S., Das, G.M. and Singh, K.K. (2005). Cross talk between mitochondria and superoxide generating NADPH oxidase in breast and ovarian tumors. Cancer Biol Ther 4, 1367-73

    Article  CAS  Google Scholar 

  • Edlund, M., Sung, S.Y. and Chung, L.W. (2004). Modulation of prostate cancer growth in bone microenvironments. J Cell Biochem 91, 686-705.

    Article  CAS  Google Scholar 

  • Eng, C., Kiuru, M., Fernandez, M.J. and Aaltonen, L.A. (2003). A role for mitochondrial enzymes in inherited neoplasia and beyond. Nat Rev Cancer 3, 193-202

    Article  CAS  Google Scholar 

  • Espineda, C.E., Chang, J.H., Twiss, J., Rajasekaran, S.A. and Rajasekaran, A.K. (2004). Repression of Na,K-ATPase beta1-subunit by the transcription factor snail in carcinoma. Mol Biol Cell 15, 1364-73

    Article  CAS  Google Scholar 

  • Falkenberg, M., Larsson, N.G. and Gustafsson, C.M. (2007). DNA replication and transcription in mammalian mitochondria. Annu Rev Biochem 76, 679-99

    Article  CAS  Google Scholar 

  • Feld, R., Rubinstein, L.V. and Weisenberger, T.H. (1984). Sites of recurrence in resected stage I non-small-cell lung cancer: a guide for future studies. J Clin Oncol 2, 1352-8

    CAS  Google Scholar 

  • Fidler, I.J. (2003). The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat Rev Cancer 3, 453-8

    Article  CAS  Google Scholar 

  • Goh, J., Enns, L., Fatemie, S., Hopkins, H., Morton, J., Pettan-Brewer, C. and Ladiges, W. (2011). Mitochondrial targeted catalase suppresses invasive breast cancer in mice. BMC Cancer 11, 191

    Article  CAS  Google Scholar 

  • Gupta, G.P. and Massague, J. (2006). Cancer metastasis: building a framework. Cell 127, 679-95

    Article  CAS  Google Scholar 

  • Hess, K.R., Varadhachary, G.R., Taylor, S.H., Wei, W., Raber, M.N., Lenzi, R. and Abbruzzese, J.L. (2006). Metastatic patterns in adenocarcinoma. Cancer 106, 1624-33

    Article  Google Scholar 

  • Hoffman, P.C., Mauer, A.M. and Vokes, E.E. (2000). Lung cancer. Lancet 355, 479-85

    CAS  Google Scholar 

  • Ishikawa, K. et al. (2008). ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis. Science 320, 661-4

    Article  CAS  Google Scholar 

  • Isidoro, A., Martinez, M., Fernandez, P.L., Ortega, A.D., Santamaria, G., Chamorro, M., Reed, J.C. and Cuezva, J.M. (2004). Alteration of the bioenergetic phenotype of mitochondria is a hallmark of breast, gastric, lung and oesophageal cancer. Biochem J 378, 17-20

    Article  CAS  Google Scholar 

  • Karbowski, M. (2010). Mitochondria on guard: role of mitochondrial fusion and fission in the regulation of apoptosis. Adv Exp Med Biol 687, 131-42

    Google Scholar 

  • Karrison, T.G., Ferguson, D.J. and Meier, P. (1999). Dormancy of mammary carcinoma after mastectomy. J Natl Cancer Inst 91, 80-5

    Article  CAS  Google Scholar 

  • Kulawiec, M., Owens, K.M. and Singh, K.K. (2009). Cancer cell mitochondria confer apoptosis resistance and promote metastasis. Cancer Biol Ther 8, 1378-85

    CAS  Google Scholar 

  • Lambert, A.J. and Brand, M.D. (2009). Reactive oxygen species production by mitochondria. Methods Mol Biol 554, 165-81

    Article  CAS  Google Scholar 

  • Lee, H.C. et al. (2005). Mitochondrial genome instability and mtDNA depletion in human cancers. Ann N Y Acad Sci 1042, 109-22

    Article  CAS  Google Scholar 

  • Mambo, E., Chatterjee, A., Xing, M., Tallini, G., Haugen, B.R., Yeung, S.C., Sukumar, S. and Sidransky, D. (2005). Tumor-specific changes in mtDNA content in human cancer. Int J Cancer 116, 920-4

    Article  CAS  Google Scholar 

  • Martinou, J.C. and Youle, R.J. (2011). Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. Dev Cell 21, 92-101

    Google Scholar 

  • Mehlen, P. and Puisieux, A. (2006). Metastasis: a question of life or death. Nat Rev Cancer 6, 449-58

    Article  CAS  Google Scholar 

  • Mizumachi, T. et al. (2008). Increased distributional variance of mitochondrial DNA content associated with prostate cancer cells as compared with normal prostate cells. Prostate 68, 408-17

    Article  CAS  Google Scholar 

  • Modica-Napolitano, J.S., Kulawiec, M. and Singh, K.K. (2007). Mitochondria and human cancer. Curr Mol Med 7, 121-31

    Article  CAS  Google Scholar 

  • Murphy, M.P. (2009). How mitochondria produce reactive oxygen species. Biochem J 417, 1-13

    Article  CAS  Google Scholar 

  • Paget, S. (1989). The distribution of secondary growths in cancer of the breast. 1889 [classical article]. Cancer & Metastasis Reviews 8, 98-101

    CAS  Google Scholar 

  • Patanaphan, V., Salazar, O.M. and Risco, R. (1988). Breast cancer: metastatic patterns and their prognosis. South Med J 81, 1109-12

    Article  CAS  Google Scholar 

  • Scatena, R. (2012). Mitochondria and cancer: a growing role in apoptosis, cancer cell metabolism and dedifferentiation. Adv Exp Med Biol 942, 287-308

    Article  CAS  Google Scholar 

  • Schmidt-Kittler, O. et al. (2003). From latent disseminated cells to overt metastasis: genetic analysis of systemic breast cancer progression. Proc Natl Acad Sci U S A 100, 7737-42

    Article  CAS  Google Scholar 

  • Selvanayagam, P. and Rajaraman, S. (1996). Detection of mitochondrial genome depletion by a novel cDNA in renal cell carcinoma. Lab Invest 74, 592-9

    CAS  Google Scholar 

  • Sotgia, F. et al. (2012). Mitochondrial metabolism in cancer metastasis: visualizing tumor cell mitochondria and the “reverse Warburg effect” in positive lymph node tissue. Cell Cycle 11, 1445-54

    Article  CAS  Google Scholar 

  • Steeg, P.S. (2006). Tumor metastasis: mechanistic insights and clinical challenges. Nat Med 12, 895-904

    Article  CAS  Google Scholar 

  • Taanman, J.W. (1999). The mitochondrial genome: structure, transcription, translation and replication. Biochim Biophys Acta 1410, 103-23

    Article  CAS  Google Scholar 

  • Tarassov, I., Kamenski, P., Kolesnikova, O., Karicheva, O., Martin, R.P., Krasheninnikov, I.A. and Entelis, N. (2007). Import of nuclear DNA-encoded RNAs into mitochondria and mitochondrial translation. Cell Cycle 6, 2473-7

    Article  CAS  Google Scholar 

  • Tseng, L.M., Yin, P.H., Chi, C.W., Hsu, C.Y., Wu, C.W., Lee, L.M., Wei, Y.H. and Lee, H.C. (2006). Mitochondrial DNA mutations and mitochondrial DNA depletion in breast cancer. Genes Chromosomes Cancer 45, 629-38

    Article  CAS  Google Scholar 

  • Weber, K., Ridderskamp, D., Alfert, M., Hoyer, S. and Wiesner, R.J. (2002). Cultivation in glucose-deprived medium stimulates mitochondrial biogenesis and oxidative metabolism in HepG2 hepatoma cells. Biol Chem 383, 283-90

    Article  CAS  Google Scholar 

  • Witkiewicz, A.K. et al. (2012). Using the "reverse Warburg effect" to identify high-risk breast cancer patients: stromal MCT4 predicts poor clinical outcome in triplenegative breast cancers. Cell Cycle 11, 1108-17

    Article  CAS  Google Scholar 

  • Yin, P.H. et al. (2004). Alteration of the copy number and deletion of mitochondrial DNA in human hepatocellular carcinoma. Br J Cancer 90, 2390-6

    CAS  Google Scholar 

  • Yu, M. et al. (2007). Reduced mitochondrial DNA copy number is correlated with tumor progression and prognosis in Chinese breast cancer patients. IUBMB Life 59, 450-7

    Article  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Department Of Pharmacological Sciences & Proteomics Center School Of Medicine, Stony Brook University, BST 8-125, Stony Brook, NY, 11794-8651, USA

    Emily I. Chen

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  1. Emily I. Chen
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Correspondence to Emily I. Chen.

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Chen, E.I. Mitochondrial dysfunction and cancer metastasis. J Bioenerg Biomembr 44, 619–622 (2012). https://doi.org/10.1007/s10863-012-9465-9

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  • DOI: https://doi.org/10.1007/s10863-012-9465-9

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