Journal
ONCOTARGET
Volume 7, Issue 26, Pages 40297-40313Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.9610
Keywords
mitochondrial DNA; Warburg effect; hypoxia; transcriptome analysis; cancer stem cells
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Funding
- Inger and John Fredriksen Foundation
- Astri and Birger Torsteds Legat
- Radium Hospital Research Foundation
- Norwegian Cancer Society
- National Natural Science Foundation of China [81272824]
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Reducing mtDNA content was considered as a critical step in the metabolism restructuring for cell stemness restoration and further neoplastic development. However, the connections between mtDNA depletion and metabolism reprograming-based cancer cell stemness in prostate cancers are still lack of studies. Here, we demonstrated that human CRPC cell line PC3 tolerated high concentration of the mtDNA replication inhibitor ethidium bromide (EtBr) and the mtDNA depletion triggered a universal metabolic remodeling process. Failure in completing that process caused lethal consequences. The mtDNA depleted (MtDP) PC3 cells could be steadily maintained in the special medium in slow cycling status. The MtDP PC3 cells contained immature mitochondria and exhibited Warburg effect. Furthermore, the MtDP PC3 cells were resistant to therapeutic treatments and contained greater cancer stem cell-like subpopulations: CD44+, ABCG2+, side-population and ALDH(bright). In conclusion, these results highlight the association of mtDNA content, mitochondrial function and cancer cell stemness features.
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