PMID- 35712500
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 12
DP  - 2022
TI  - Stable Isotope Tracing Uncovers Reduced gamma/beta-ATP Turnover and Metabolic Flux 
      Through Mitochondrial-Linked Phosphotransfer Circuits in Aggressive Breast Cancer 
      Cells.
PG  - 892195
LID - 10.3389/fonc.2022.892195 [doi]
LID - 892195
AB  - Changes in dynamics of ATP gamma- and beta-phosphoryl turnover and metabolic flux 
      through phosphotransfer pathways in cancer cells are still unknown. Using (18)O 
      phosphometabolite tagging technology, we have discovered phosphotransfer dynamics 
      in three breast cancer cell lines: MCF7 (non-aggressive), MDA-MB-231 
      (aggressive), and MCF10A (control). Contrary to high intracellular ATP levels, 
      the (18)O labeling method revealed a decreased gamma- and beta-ATP turnover in both 
      breast cancer cells, compared to control. Lower beta-ATP[(18)O] turnover indicates 
      decreased adenylate kinase (AK) flux. Aggressive cancer cells had also reduced 
      fluxes through hexokinase (HK) G-6-P[(18)O], creatine kinase (CK) [CrP[(18)O], 
      and mitochondrial G-3-P[(18)O] substrate shuttle. Decreased CK metabolic flux was 
      linked to the downregulation of mitochondrial MTCK1A in breast cancer cells. 
      Despite the decreased overall phosphoryl flux, overexpression of HK2, AK2, and 
      AK6 isoforms within cell compartments could promote aggressive breast cancer 
      growth.
CI  - Copyright (c) 2022 Klepinin, Miller, Reile, Puurand, Rebane-Klemm, Klepinina, Vija, 
      Zhang, Terzic, Dzeja and Kaambre.
FAU - Klepinin, Aleksandr
AU  - Klepinin A
AD  - Laboratory of Chemical Biology, National Institute of Chemical Physics and 
      Biophysics, Tallinn, Estonia.
AD  - Department of Cardiovascular Medicine and Center for Regenerative Medicine, Mayo 
      Clinic, Rochester, MN, United States.
FAU - Miller, Sten
AU  - Miller S
AD  - Laboratory of Chemical Biology, National Institute of Chemical Physics and 
      Biophysics, Tallinn, Estonia.
AD  - Department of Chemistry and Biotechnology, School of Science, Tallinn University 
      of Technology, Tallinn, Estonia.
FAU - Reile, Indrek
AU  - Reile I
AD  - Laboratory of Chemical Physics, National Institute of Chemical Physics and 
      Biophysics, Tallinn, Estonia.
FAU - Puurand, Marju
AU  - Puurand M
AD  - Laboratory of Chemical Biology, National Institute of Chemical Physics and 
      Biophysics, Tallinn, Estonia.
FAU - Rebane-Klemm, Egle
AU  - Rebane-Klemm E
AD  - Laboratory of Chemical Biology, National Institute of Chemical Physics and 
      Biophysics, Tallinn, Estonia.
AD  - Department of Chemistry and Biotechnology, School of Science, Tallinn University 
      of Technology, Tallinn, Estonia.
FAU - Klepinina, Ljudmila
AU  - Klepinina L
AD  - Laboratory of Chemical Biology, National Institute of Chemical Physics and 
      Biophysics, Tallinn, Estonia.
AD  - Department of Chemistry and Biotechnology, School of Science, Tallinn University 
      of Technology, Tallinn, Estonia.
FAU - Vija, Heiki
AU  - Vija H
AD  - Laboratory of Environmental Toxicology, National Institute of Chemical Physics 
      and Biophysics, Tallinn, Estonia.
FAU - Zhang, Song
AU  - Zhang S
AD  - Department of Cardiovascular Medicine and Center for Regenerative Medicine, Mayo 
      Clinic, Rochester, MN, United States.
FAU - Terzic, Andre
AU  - Terzic A
AD  - Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 
      Rochester, MN, United States.
AD  - Department of Clinical Genomics, Mayo Clinic, Rochester, MN, United States.
FAU - Dzeja, Petras
AU  - Dzeja P
AD  - Department of Cardiovascular Medicine and Center for Regenerative Medicine, Mayo 
      Clinic, Rochester, MN, United States.
FAU - Kaambre, Tuuli
AU  - Kaambre T
AD  - Laboratory of Chemical Biology, National Institute of Chemical Physics and 
      Biophysics, Tallinn, Estonia.
LA  - eng
PT  - Journal Article
DEP - 20220531
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC9194814
OTO - NOTNLM
OT  - 18 O stable isotope labeling technology
OT  - adenylate kinase
OT  - creatine kinase
OT  - glycolysis
OT  - oxidative phosphorylation
OT  - phosphotransfer network
OT  - triple-negative breast cancer
OT  - gamma-and beta-ATP phosphoryl turnover
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/06/18 06:00
MHDA- 2022/06/18 06:01
PMCR- 2022/05/31
CRDT- 2022/06/17 02:42
PHST- 2022/03/08 00:00 [received]
PHST- 2022/05/03 00:00 [accepted]
PHST- 2022/06/17 02:42 [entrez]
PHST- 2022/06/18 06:00 [pubmed]
PHST- 2022/06/18 06:01 [medline]
PHST- 2022/05/31 00:00 [pmc-release]
AID - 10.3389/fonc.2022.892195 [doi]
PST - epublish
SO  - Front Oncol. 2022 May 31;12:892195. doi: 10.3389/fonc.2022.892195. eCollection 
      2022.