title: MtDNA depleted PC3 cells exhibit Warburg effect and cancer stem cell features.
abstract: 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 ALDHbright. In conclusion, these results highlight the association of mtDNA content, mitochondrial function and cancer cell stemness features.
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, 0379, Norway.|Department of Pathology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, 0318, Norway.
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, 450052, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, 450001, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Urology, The Akershus University Hospital, Lørenskog, 1478, Norway.
authors.forename: Karol
authors.initials: K
authors.lastname: Axcrona
authors.affiliation: Department of Medical Biochemistry, University of Oslo and Oslo University Hospital, Oslo, 0372, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Eide
authors.affiliation: Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, 0379, Norway.
authors.forename: Randi G
authors.initials: RG
authors.lastname: Syljuåsen
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, 0379, Norway.
authors.forename: Qian
authors.initials: Q
authors.lastname: Peng
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, 0379, Norway.
authors.forename: Junbai
authors.initials: J
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing, 100191, China.
authors.forename: Hongquan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Surgery, The Norwegian Radium Hospital, Oslo University Hospital, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, 0379, Norway.
authors.forename: Mariusz Adam
authors.initials: MA
authors.lastname: Goscinski
authors.affiliation: Department of Cell Therapy, Cancer Institute, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, 0379, Norway.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Kvalheim
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, 0379, Norway.|Department of Pathology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, 0318, Norway.
authors.forename: Jahn M
authors.initials: JM
authors.lastname: Nesland
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, 0379, Norway.|Department of Pathology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, 0318, Norway.
authors.forename: Zhenhe
authors.initials: Z
authors.lastname: Suo
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000378:metabolism; D002452:Cell Count; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D004261:DNA Replication / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000235:genetics*; D004996:Ethidium / Q000737:chemistry; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000166:cytology*; D010100:Oxygen / Q000737:chemistry; D010101:Oxygen Consumption; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; C497483:CD44 protein, human; D004272:DNA, Mitochondrial; D018960:Hyaluronan Receptors; D009363:Neoplasm Proteins; D004996:Ethidium; D010100:Oxygen
keywords: Warburg effect; cancer stem cells; hypoxia; mitochondrial DNA; transcriptome analysis