Skip to main content

Advertisement

SpringerLink
Log in

Metabolic reprogramming of mitochondrial respiration in metastatic cancer

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

Tumor initiation, progression, and metastasis are tissue context-dependent processes. Cellular and non-cellular factors provide the selective microenvironment that determines the fate of the evolving tumor through mechanisms that include metabolic reprogramming. Genetic and epigenetic changes contribute to this reprogramming process, which is orchestrated through ongoing communication between the mitochondrial and nuclear genomes. Metabolic flexibility, in particular the ability to rapidly adjust the balance between glycolytic and mitochondrial energy production, is a hallmark of aggressive, invasive, and metastatic cancers. Tumor cells sustain damage to both nuclear and mitochondrial DNA during tumorigenesis and as a consequence of anticancer treatments. Nuclear and mitochondrial DNA mutations and polymorphisms are increasingly recognized as factors that influence metabolic reprogramming, tumorigenesis, and tumor progression. Severe mitochondrial DNA damage compromises mitochondrial respiration. When mitochondrial respiration drops below a cell-specific threshold, metabolic reprogramming and plasticity fail to compensate and tumor formation is compromised. In these scenarios, tumorigenesis can be restored by acquisition of respiring mitochondria from surrounding stromal cells. Thus, intercellular mitochondrial transfer has the potential to confer treatment resistance and to promote tumor progression and metastasis. Understanding the constraints of metabolic, and in particular bioenergetic reprogramming, and the role of intercellular mitochondrial transfer in tumorigenesis provides new insights into addressing tumor progression and treatment resistance in highly aggressive cancers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Wu, F., & Minteer, S. (2015). Krebs cycle metabolon: Structural evidence of substrate channeling revealed by cross-linking and mass spectrometry. Angewandte Chemie, International Edition, 54(6), 1851–1854.

    Article  CAS  Google Scholar 

  2. Ahn, C., & Metallo, C. (2015). Mitochondria as biosynthetic factories for cancer proliferation. Cancer & Metabolism, 3(1), 1–10.

    Article  Google Scholar 

  3. Smolková, K., Plecitá-Hlavatá, L., Bellance, N., Benard, G., Rossignol, R., & Ježek, P. (2011). Waves of gene regulation suppress and then restore oxidative phosphorylation in cancer cells. The International Journal of Biochemistry & Cell Biology, 43(7), 950–968.

    Article  CAS  Google Scholar 

  4. Wallace, D., Fan, W., & Procaccio, V. (2010). Mitochondrial energetics and therapeutics. Annual Review of Pathology, 5, 297–348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Wallace, D. (2016). Mitochondrial DNA in aging and disease. Nature, 535(7613), 498–500.

    Article  CAS  PubMed  Google Scholar 

  6. Coppotelli, G., & Ross, J. (2016). Mitochondria in Ageing and Diseases: The Super Trouper of the Cell. International Journal of Molecular Sciences, 17(5), 711 (1–5).

    Article  PubMed Central  CAS  Google Scholar 

  7. Deberardinis, R., & Chandel, N. (2016). Fundamentals of cancer metabolism. Oncology, 2(5), e1600200.

    Google Scholar 

  8. Halestrap, A., & Richardson, A. (2015). The mitochondrial permeability transition: A current perspective on its identity and role in ischaemia/reperfusion injury. Journal of Molecular and Cellular Cardiology, 78, 129–141.

    Article  CAS  PubMed  Google Scholar 

  9. Simula, L., Nazio, F., & Campello, S. (2017). The mitochondrial dynamics in cancer and immune-surveillance. Seminars in Cancer Biology, 47(December 2016), 29–42.

    Article  CAS  PubMed  Google Scholar 

  10. Giorgi, C., Missiroli, S., Patergnani, S., Duszynski, J., Wieckowski, M., & Pinton, P. (2015). Mitochondria-associated membranes: Composition, molecular mechanisms, and Physiopathological implications. Antioxidants & Redox Signaling, 22(12), 995–1019.

    Article  CAS  Google Scholar 

  11. Missiroli, S., Patergnani, S., Caroccia, N., Pedriali, G., Perrone, M., Previati, M., et al. (2018). Mitochondria-associated membranes (MAMs) and inflammation. Cell Death & Disease, 9(3), 329.

    Article  CAS  Google Scholar 

  12. Wang, J., Liu, X., Qiu, Y., Shi, Y., Cai, J., Wang, B., Wei, X., Ke, Q., Sui, X., Wang, Y., Huang, Y., Li, H., Wang, T., Lin, R., Liu, Q., & Xiang, A. P. (2018). Cell adhesion-mediated mitochondria transfer contributes to mesenchymal stem cell-induced chemoresistance on T cell acute lymphoblastic leukemia cells. Journal of Hematology & Oncology, 11(1), 1–13.

    Article  CAS  Google Scholar 

  13. Gottlieb, R., & Stotland, A. (2015). MitoTimer: A novel protein for monitoring mitochondrial turnover in the heart. Journal of Molecular Medicine, 93(3), 271–278.

    Article  CAS  PubMed  Google Scholar 

  14. Youle, R., & Narendra, D. (2011). Mechanisms of mitophagy. Nature Reviews. Molecular Cell Biology, 12(1), 9–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Taanman, J.-W. (1999). The mitochondrial genome: Structure, transcription, translation and replication. Biochimica et Biophysica Acta, Bioenergetics, 1410, 103–123.

    Article  CAS  Google Scholar 

  16. Hensen, F., Cansiz, S., Gerhold, J., & Spelbrink, J. (2014). To be or not to be a nucleoid protein: A comparison of mass-spectrometry based approaches in the identification of potential mtDNA-nucleoid associated proteins. Biochimie, 100(1), 219–226.

    Article  CAS  PubMed  Google Scholar 

  17. Arnould, T., Michel, S., & Renard, P. (2015). Mitochondria retrograde signaling and the UPR mt: Where are we in mammals? International Journal of Molecular Sciences, 16(8), 18224–18251.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Mookerjee, S. A., Gerencser, A. A., Nicholls, D. G., & Brand, M. D. (2017). Quantifying intracellular rates of glycolytic and oxidative ATP production and consumption using extracellular flux measurements. The Journal of Biological Chemistry, 292(17), 7189–7207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Herst, P. M., Tan, A. S., Scarlett, D.-J. G., & Berridge, M. V. (2004). Cell surface oxygen consumption by mitochondrial gene knockout cells. Biochimica et Biophysica Acta, 1656(2–3), 79–87.

    Article  CAS  PubMed  Google Scholar 

  20. Herst, P., & Berridge, M. (2007). Cell surface oxygen consumption: A major contributor to cellular oxygen consumption in glycolytic cancer cell lines. Biochimica et Biophysica Acta, Bioenergetics, 1767(2), 170–177.

    Article  CAS  Google Scholar 

  21. Herst, P., & Berridge, M. (2006). Plasma membrane electron transport: A new target for cancer drug development. Current Molecular Medicine, 6, 895–904.

    Article  CAS  PubMed  Google Scholar 

  22. Scarlett, D., Herst, P., Tan, A., Prata, C., & Berridge, M. (2004). Mitochondrial gene-knockout (rho0) cells: A versatile model for exploring the secrets of trans-plasma membrane electron transport. BioFactors, 20(4), 199–206.

    Article  PubMed  Google Scholar 

  23. Courtnay, R., Ngo, D., Malik, N., Ververis, K., Tortorella, S., & Karagiannis, T. (2015). Cancer metabolism and the Warburg effect: The role of HIF-1 and PI3K. Molecular Biology Reports, 42(4), 841–851.

    Article  CAS  PubMed  Google Scholar 

  24. Guerra, F., Arbini, A., & Moro, L. (2017). Mitochondria and cancer chemoresistance. Biochimica et Biophysica Acta, Bioenergetics, 1858(8), 686–699.

    Article  CAS  PubMed  Google Scholar 

  25. Quinlan, C., Perevoshchikova, I., Orr, A., & Brand, M. (2013). Sites of reactive oxygen species generation by mitochondria oxidizing different substrates. Redox Biology, 1(1), 304–312.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chen, Y., Zhang, H., Zhou, H., Ji, W., & Min, W. (2016). Mitochondrial redox signaling and tumor progression. Cancers (Basel)., 8(4), 1–15.

    Article  CAS  Google Scholar 

  27. Holzerová, E., & Prokisch, H. (2015). Mitochondria: Much ado about nothing? How dangerous is reactive oxygen species production? The International Journal of Biochemistry & Cell Biology, 63, 16–20.

    Article  CAS  Google Scholar 

  28. Dikalov, S. (2011). Crosstalk between mitochondria and NADPH oxidases. Free Radical Biology & Medicine, 51(7), 1289–1301.

    Article  CAS  Google Scholar 

  29. Warburg, O. (1956). On the origin of cancer ells. Nature, 123(3191), 309–314.

    CAS  Google Scholar 

  30. Heiden Vander, M. G., Cantley, L., & Thompson, C. (2009). Understanding the Warburg Effect : Cell Proliferation. Science, 324(May), 1029.

    Article  CAS  Google Scholar 

  31. Gatenby, R., & Gillies, R. (2004). Why do cancers have high aerobic glycolysis? Nature Reviews Cancer, 4(11), 891–899.

    Article  CAS  PubMed  Google Scholar 

  32. Porporato, P., Payen, V., Pérez-Escuredo, J., De Saedeleer, C., Danhier, P., Copetti, T., et al. (2014). A mitochondrial switch promotes tumor metastasis. Cell Reports, 8(3), 754–766.

    Article  CAS  PubMed  Google Scholar 

  33. Carelli, V., Maresca, A., Caporali, L., Trifunov, S., Zanna, C., & Rugolo, M. (2015). Mitochondria: Biogenesis and mitophagy balance in segregation and clonal expansion of mitochondrial DNA mutations. The International Journal of Biochemistry & Cell Biology, 63, 21–24.

    Article  CAS  Google Scholar 

  34. Busch, K., Kowald, A., & Spelbrink, J. (2014). Quality matters: How does mitochondrial network dynamics and quality control impact on mtDNA integrity? Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 369(1646), 20130442.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Gumeni, S., & Trougakos, I. (2016). Cross talk of Proteostasis and Mitostasis in cellular Homeodynamics, ageing, and disease. Oxidative Medicine and Cellular Longevity, 2016, 1–24.

    Article  CAS  Google Scholar 

  36. Sun, X., & St. John, J. C. (2016). The role of the mtDNA set point in differentiation, development and tumorigenesis. The Biochemical Journal, 473(19), 2955–2971.

    Article  CAS  PubMed  Google Scholar 

  37. van Gisbergen, M. W., Voets, A. M., Starmans, M. H. W., de Coo, I. F. M., Yadak, R., Hoffmann, R. F., Boutros, P. C., Smeets, H. J. M., Dubois, L., & Lambin, P. (2015). How do changes in the mtDNA and mitochondrial dysfunction influence cancer and cancer therapy? Challenges, opportunities and models. Mutation Research, Reviews in Mutation Research, 764, 16–30.

    Article  PubMed  CAS  Google Scholar 

  38. Picard, M., Wallace, D. C., & Burelle, Y. (2016). The rise of mitochondria in medicine. Mitochondrion, 30, 105–116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Singh, B., Modica-Napolitano, J., & Singh, K. (2017). Defining the momiome: Promiscuous information transfer by mobile mitochondria and the mitochondrial genome. Seminars in Cancer Biology, 47(April), 1–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Tuppen, H., Blakely, E., Turnbull, D., & Taylor, R. (2010). Mitochondrial DNA mutations and human disease. Biochimica et Biophysica Acta, 1797(2), 113–128.

    Article  CAS  PubMed  Google Scholar 

  41. Garrido, N., Griparic, L., Jokitalo, E., Wartiovaara, J., van der Bliek, A., & Spelbrink, J. N. (2003). Composition and dynamics of human mitochondrial nucleoids. Molecular Biology of the Cell, 14(4), 1583–1596.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Guliaeva, N., Kuznetsova, E., & Gaziev, A. (2006). Proteins associated with mitochon- drial DNA protect it against the action of X-rays and hydrogen peroxide. Biofizika, 51(4), 692–697.

    CAS  PubMed  Google Scholar 

  43. Twig, G., & Shirihai, O. G. (2011). The interplay between mitochondrial dynamics and mitophagy. Antioxidants & Redox Signaling, 14(10), 1939–1951.

    Article  CAS  Google Scholar 

  44. Iommarini, L., Kurelac, I., Capristo, M., Calvaruso, M., Giorgio, V., Bergamini, C., et al. (2014). Different mtDNA mutations modify tumor progression in dependence of the degree of respiratory complex I impairment. Human Molecular Genetics, 23(6), 1453–1466.

    Article  CAS  PubMed  Google Scholar 

  45. Wallace, D., & Mitochondrial, D. N. A. (2015). Variation in human radiation and disease. Cell, 163(1), 33–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kenney, M. C., Chwa, M., Atilano, S. R., Falatoonzadeh, P., Ramirez, C., Malik, D., Tarek, M., del Carpio, J. C., Nesburn, A. B., Boyer, D. S., Kuppermann, B. D., Vawter, M. P., Jazwinski, S. M., Miceli, M. V., Wallace, D. C., & Udar, N. (2014). Molecular and bioenergetic differences between cells with African versus European inherited mitochondrial DNA haplogroups: Implications for population susceptibility to diseases. Biochimica et Biophysica Acta, Molecular Basis of Disease, 1842(2), 208–219.

    Article  CAS  Google Scholar 

  47. Ishikawa, K., Takenaga, K., Akimoto, M., Koshikawa, N., Yamaguchi, A., Imanishi, H., et al. (2008). ROS-Generating Mitochondrial DNA Mutations Can Regulate Tumor Cell Metastasis. Science, 320(5876), 661–664.

    Article  CAS  PubMed  Google Scholar 

  48. Tan, A., Baty, J., Dong, L., Bezawork-Geleta, A., Endaya, B., Goodwin, J., et al. (2015). Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA. Cell Metabolism, 21(1), 81–94.

    Article  CAS  PubMed  Google Scholar 

  49. Bayona-Bafaluy, M., Acín-Pérez, R., Mullikin, J., Park, J., Moreno-Loshuertos, R., Hu, P., et al. (2003). Revisiting the mouse mitochondrial DNA sequence. Nucleic Acids Research, 31(18), 5349–5355.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Brinker, A., Vivian, C., Koestler, D., Tsue, T., Jensen, R., & Welch, D. (2017). Mitochondrial haplotype alters mammary cancer tumorigenicity and metastasis in an oncogenic driver–dependent manner. Cancer Research, 77(24), 6941–6949.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Hunter, K., Amin, R., Deasy, S., Ha, N., & Wakefield, L. (2018). Genetic insights into the morass of metastatic heterogeneity. Nature Reviews Cancer, 18(4), 211–223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Vivian, C., Brinker, A., Graw, S., Koestler, D., Legendre, C., Gooden, G., et al. (2017). Mitochondrial genomic backgrounds affect nuclear DNA methylation and gene expression. Cancer Research, 77(22), 6202–6214.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Sun, X., Johnson, J., & St John, J. (2018). Global DNA methylation synergistically regulates the nuclear and mitochondrial genomes in glioblastoma cells. Nucleic Acids Research, 46(12), 5977–5995.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Dong, L., Kovarova, J., Bajzikova, M., Bezawork-Geleta, A., Svec, D., Endaya, B., et al. (2017). Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells. eLife, 6.

  55. Lee, W., Sun, X., Tsai, T.-S., Johnson, J., Gould, J., Garama, D., et al. (2017). Mitochondrial DNA haplotypes induce differential patterns of DNA methylation that result in differential chromosomal gene expression patterns. Cell Death & Disease, 3(August), 17062.

    Article  CAS  Google Scholar 

  56. Danhier, P., Bański, P., Payen, V., Grasso, D., Ippolito, L., Sonveaux, P., et al. (2017). Cancer metabolism in space and time: Beyond the Warburg effect. Biochimica et Biophysica Acta, Bioenergetics, 1858(8), 556–572.

    Article  CAS  PubMed  Google Scholar 

  57. Jose, C., Bellance, N., & Rossignol, R. (2011). Choosing between glycolysis and oxidative phosphorylation: A tumor’s dilemma? Biochimica et Biophysica Acta, Bioenergetics, 1807(6), 552–561.

    Article  CAS  Google Scholar 

  58. Ventura-Clapier, R., Garnier, A., & Veksler, V. (2008). Transcriptional control of mitochondrial biogenesis: The central role of PGC-1alpha. Cardiovascular Research, 79(2), 208–217.

    Article  CAS  PubMed  Google Scholar 

  59. Berridge, M., & Herst, P. (2015). Tumor cell complexity and metabolic flexibility in tumorigenesis and metastasis. In S. Mazurek & M. Shoshan (Eds.), Tumor cell metabolism (p. 23–43). Vienna: Springer.

    Google Scholar 

  60. Ralph, S., Rodríguez-Enríquez, S., Neuzil, J., & Moreno-Sánchez, R. (2010). Bioenergetic pathways in tumor mitochondria as targets for cancer therapy and the importance of the ROS-induced apoptotic trigger. Molecular Aspects of Medicine, 31(1), 29–59.

    Article  CAS  PubMed  Google Scholar 

  61. Herst, P., Dawson, R., & Berridge, M. (2018). Intercellular Communication in Tumor Biology: A Role for Mitochondrial Transfer. Frontiers in Oncology, 8(August), 344.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Spees, J., Lee, R., & Gregory, C. (2016). Mechanisms of mesenchymal stem/stromal cell function. Stem Cell Research & Therapy, 7(1), 125.

    Article  CAS  Google Scholar 

  63. Su, S., Chen, J., Yao, H., Liu, J., Yu, S., Lao, L., et al. (2018). CD10+GPR77+Cancer-Associated Fibroblasts Promote Cancer Formation and Chemoresistance by Sustaining Cancer Stemness. Cell, 172(4), 841–856.e16.

    Article  CAS  PubMed  Google Scholar 

  64. LeBleu, V., & Kalluri, R. (2018). A peek into cancer-associated fibroblasts: origins, functions and translational impact. Disease Models & Mechanisms, 11(4), dmm029447.

    Article  CAS  Google Scholar 

  65. Kalluri, R. (2016). The biology and function of fibroblasts in cancer. Nature Reviews. Cancer, 16(9), 582–598.

    Article  CAS  PubMed  Google Scholar 

  66. Costa, A., Kieffer, Y., Scholer-Dahirel, A., Pelon, F., Bourachot, B., Cardon, M., et al. (2018). Fibroblast Heterogeneity and Immunosuppressive Environment in Human Breast Cancer. Cancer Cell, 33(3), 463–479.e10.

    Article  CAS  PubMed  Google Scholar 

  67. Liao, Z., Tan, Z., Zhu, P., & Tan, N. (2018). Cancer-associated fibroblasts in tumor microenvironment - accomplices in tumor malignancy. Cellular Immunology, (September 2017), 0–1.

  68. Barnes, T., & Amir, E. (2017). HYPE or HOPE: The prognostic value of infiltrating immune cells in cancer. British Journal of Cancer, 117(4), 451–460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. King, M. P., & Attardi, G. (1989). Human cells lacking mtDNA: Repopulation with exogenous mitochondria by complementation. Science, 246(4929), 500–503.

    Article  CAS  PubMed  Google Scholar 

  70. Larm, J. A., Vaillant, F., Linnane, A. W., & Lawen, A. (1994). Up-regulation of the plasma membrane oxidoreductase as a prerequisite for viability of human Nawala Ro cells. The Journal of Biological Chemistry, 269, 30097–30100.

    CAS  PubMed  Google Scholar 

  71. Spees, J., Olson, S., Whitney, M., & Prockop, D. (2006). Mitochondrial transfer between cells can rescue aerobic respiration. Proceedings of the National Academy of Sciences, 103(5), 1283–1288.

    Article  CAS  Google Scholar 

  72. Berridge, M., Dong, L., & Neuzil, J. (2015). Mitochondrial DNA in tumor initiation, progression, and metastasis: Role of horizontal mtDNA transfer. Cancer Research, 75(16), 3203–3208.

    Article  CAS  PubMed  Google Scholar 

  73. Rodriguez, A., Nakhle, J., Griessinger, E., & Vignais, M. (2018). Intercellular mitochondria trafficking highlighting the dual role of mesenchymal stem cells as both sensors and rescuers of tissue injury. Cell Cycle, 17(6), 712–721.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Berridge, M. V., & Tan, A. S. (2010). Effects of mitochondrial gene deletion on tumorigenicity of metastatic melanoma: Reassessing the Warburg effect. Rejuvenation Research, 13(2–3), 139–141.

    Article  CAS  PubMed  Google Scholar 

  75. Caicedo, A., Fritz, V., Brondello, J.-M., Ayala, M., Dennemont, I., Abdellaoui, N., de Fraipont, F., Moisan, A., Prouteau, C. A., Boukhaddaoui, H., Jorgensen, C., & Vignais, M. L. (2015). MitoCeption as a new tool to assess the effects of mesenchymal stem/stromal cell mitochondria on cancer cell metabolism and function. Scientific Reports, 5(1), 9073.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Davis, C., Kim, K.-Y., Bushong, E., Mills, E., Boassa, D., Shih, T., et al. (2014). Transcellular degradation of axonal mitochondria. Proceedings of the National Academy of Sciences of the United States of America, 111(26), 9633–9638.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Lee, W., Cain, J., Cuddihy, A., Johnson, J., Dickinson, A., Yeung, K.-Y., et al. (2016). Mitochondrial DNA plasticity is an essential inducer of tumorigenesis. Cell Death & Disease, 2(January), 16016.

    Article  CAS  Google Scholar 

  78. Moschoi, R., Imbert, V., Nebout, M., Chiche, J., Mary, D., Prebet, T., Saland, E., Castellano, R., Pouyet, L., Collette, Y., Vey, N., Chabannon, C., Recher, C., Sarry, J. E., Alcor, D., Peyron, J. F., & Griessinger, E. (2016). Protective mitochondrial transfer from bone marrow stromal cells to acute myeloid leukemic cells during chemotherapy. Blood, 128, 253–264.

    Article  CAS  PubMed  Google Scholar 

  79. Marlein, C., Zaitseva, L., Piddock, R., Robinson, S., Edwards, D., Shafat, M., et al. (2017). NADPH oxidase-2 derived superoxide drives mitochondrial transfer from bone marrow stromal cells to leukemic blasts. Blood, 130(14), 1649–1660.

    CAS  PubMed  Google Scholar 

  80. Kulawiec, M., Safina, A., Desouki, M., Still, I., Matsui, S.-I., Bakin, A., et al. (2008). Tumorigenic transformation of human breast epithelial cells induced by mitochondrial DNA depletion. Cancer Biology & Therapy, 7(11), 1732–1743.

    Article  CAS  Google Scholar 

  81. Tran, Q., Lee, H., Park, J., Kim, S.-H., & Park, J. (2016). Targeting Cancer metabolism - revisiting the Warburg effects. Toxicology Research, 32(3), 177–193.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We acknowledge unpublished mouse tumor mtDNA sequence information from Matt Rowe and Georgia Carson.

Funding

The authors received author salary support from the Health Research Council of NZ, the Cancer Society of NZ, the Malaghan Institute (MVB, CG) and the University of Otago, Wellington (PH).

Author information

Authors and Affiliations

  1. Malaghan Institute of Medical Research, PO Box 7060, Wellington, 6242, New Zealand

    P. M. Herst, C. Grasso & Michael V. Berridge

  2. Department of Radiation Therapy, University of Otago, Wellington, New Zealand

    P. M. Herst

Authors
  1. P. M. Herst
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Grasso
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael V. Berridge
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MVB and PH planned and wrote the review; CG prepared Table 1, contributed to Fig. 1 and to parts of the text, and all authors contributed to editing and revision.

Corresponding author

Correspondence to Michael V. Berridge.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Herst, P.M., Grasso, C. & Berridge, M.V. Metabolic reprogramming of mitochondrial respiration in metastatic cancer. Cancer Metastasis Rev 37, 643–653 (2018). https://doi.org/10.1007/s10555-018-9769-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10555-018-9769-2

Keywords

Search

Navigation