Role of mitochondrial dysfunction in cancer progression
- PMID: 27022139
- PMCID: PMC4950268
- DOI: 10.1177/1535370216641787
Role of mitochondrial dysfunction in cancer progression
Abstract
Deregulated cellular energetics was one of the cancer hallmarks. Several underlying mechanisms of deregulated cellular energetics are associated with mitochondrial dysfunction caused by mitochondrial DNA mutations, mitochondrial enzyme defects, or altered oncogenes/tumor suppressors. In this review, we summarize the current understanding about the role of mitochondrial dysfunction in cancer progression. Point mutations and copy number changes are the two most common mitochondrial DNA alterations in cancers, and mitochondrial dysfunction induced by chemical depletion of mitochondrial DNA or impairment of mitochondrial respiratory chain in cancer cells promotes cancer progression to a chemoresistance or invasive phenotype. Moreover, defects in mitochondrial enzymes, such as succinate dehydrogenase, fumarate hydratase, and isocitrate dehydrogenase, are associated with both familial and sporadic forms of cancer. Deregulated mitochondrial deacetylase sirtuin 3 might modulate cancer progression by regulating cellular metabolism and oxidative stress. These mitochondrial defects during oncogenesis and tumor progression activate cytosolic signaling pathways that ultimately alter nuclear gene expression, a process called retrograde signaling. Changes in the intracellular level of reactive oxygen species, Ca(2+), or oncometabolites are important in the mitochondrial retrograde signaling for neoplastic transformation and cancer progression. In addition, altered oncogenes/tumor suppressors including hypoxia-inducible factor 1 and tumor suppressor p53 regulate mitochondrial respiration and cellular metabolism by modulating the expression of their target genes. We thus suggest that mitochondrial dysfunction plays a critical role in cancer progression and that targeting mitochondrial alterations and mitochondrial retrograde signaling might be a promising strategy for the development of selective anticancer therapy.
Keywords: Cancer; DNA; carcinogenesis; medicine/oncology; metabolism; mitochondrial.
© 2016 by the Society for Experimental Biology and Medicine.
Figures
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4950268/bin/10.1177_1535370216641787-fig1.gif)
![Figure 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4950268/bin/10.1177_1535370216641787-fig2.gif)
Similar articles
-
Genetic alterations in Krebs cycle and its impact on cancer pathogenesis.Biochimie. 2017 Apr;135:164-172. doi: 10.1016/j.biochi.2017.02.008. Epub 2017 Feb 20. Biochimie. 2017. PMID: 28219702 Review.
-
Mitochondria in cancer: at the crossroads of life and death.Chin J Cancer. 2011 Aug;30(8):526-39. doi: 10.5732/cjc.011.10018. Chin J Cancer. 2011. PMID: 21801601 Free PMC article. Review.
-
Somatic mutations of mitochondrial DNA in aging and cancer progression.Ageing Res Rev. 2010 Nov;9 Suppl 1:S47-58. doi: 10.1016/j.arr.2010.08.009. Epub 2010 Sep 8. Ageing Res Rev. 2010. PMID: 20816876 Review.
-
Mitochondrial dysfunctions in cancer: genetic defects and oncogenic signaling impinging on TCA cycle activity.Cancer Lett. 2015 Jan 28;356(2 Pt A):217-23. doi: 10.1016/j.canlet.2014.02.023. Epub 2014 Mar 12. Cancer Lett. 2015. PMID: 24614286 Review.
-
Mitochondrial determinants of cancer health disparities.Semin Cancer Biol. 2017 Dec;47:125-146. doi: 10.1016/j.semcancer.2017.05.001. Epub 2017 May 6. Semin Cancer Biol. 2017. PMID: 28487205 Free PMC article. Review.
Cited by
-
Safety, tolerability and toxicokinetics of the novel mitochondrial drug SUL-138 administered orally to rat and minipig.Toxicol Rep. 2024 Mar 19;12:345-355. doi: 10.1016/j.toxrep.2024.03.009. eCollection 2024 Jun. Toxicol Rep. 2024. PMID: 38560508 Free PMC article.
-
Putative Molecular Mechanisms Underpinning the Inverse Roles of Mitochondrial Respiration and Heme Function in Lung Cancer and Alzheimer's Disease.Biology (Basel). 2024 Mar 14;13(3):185. doi: 10.3390/biology13030185. Biology (Basel). 2024. PMID: 38534454 Free PMC article. Review.
-
The movement of mitochondria in breast cancer: internal motility and intercellular transfer of mitochondria.Clin Exp Metastasis. 2024 Mar 15. doi: 10.1007/s10585-024-10269-3. Online ahead of print. Clin Exp Metastasis. 2024. PMID: 38489056 Review.
-
Anti-Cancer Potency of Copper-Doped Carbon Quantum Dots Against Breast Cancer Progression.Int J Nanomedicine. 2024 Feb 27;19:1985-2004. doi: 10.2147/IJN.S449887. eCollection 2024. Int J Nanomedicine. 2024. PMID: 38435754 Free PMC article.
-
Vitamin D-mediated tsRNA-07804 triggers mitochondrial dysfunction and suppresses non-small cell lung cancer progression by targeting CRKL.J Cancer Res Clin Oncol. 2024 Jan 30;150(2):51. doi: 10.1007/s00432-023-05586-1. J Cancer Res Clin Oncol. 2024. PMID: 38289488 Free PMC article.
References
-
- Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144: 646–74. - PubMed
-
- Chen Z, Lu W, Garcia-Prieto C, Huang P. The Warburg effect and its cancer therapeutic implications. J Bioenerg Biomembr 2007; 39: 267–74. - PubMed
-
- Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer 2011; 11: 85–95. - PubMed
-
- Upadhyay M, Samal J, Kandpal M, Singh OV, Vivekanandan P. The Warburg effect: insights from the past decade. Pharmacol Ther 2013; 137: 318–30. - PubMed
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous