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Stable Isotope Tracing Uncovers Reduced γ/β-ATP Turnover and Metabolic Flux Through Mitochondrial-Linked Phosphotransfer Circuits in Aggressive Breast Cancer Cells

Changes in dynamics of ATP γ- and β-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-M...

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Autores principales: Klepinin, Aleksandr, Miller, Sten, Reile, Indrek, Puurand, Marju, Rebane-Klemm, Egle, Klepinina, Ljudmila, Vija, Heiki, Zhang, Song, Terzic, Andre, Dzeja, Petras, Kaambre, Tuuli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194814/
https://www.ncbi.nlm.nih.gov/pubmed/35712500
http://dx.doi.org/10.3389/fonc.2022.892195
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author Klepinin, Aleksandr
Miller, Sten
Reile, Indrek
Puurand, Marju
Rebane-Klemm, Egle
Klepinina, Ljudmila
Vija, Heiki
Zhang, Song
Terzic, Andre
Dzeja, Petras
Kaambre, Tuuli
author_facet Klepinin, Aleksandr
Miller, Sten
Reile, Indrek
Puurand, Marju
Rebane-Klemm, Egle
Klepinina, Ljudmila
Vija, Heiki
Zhang, Song
Terzic, Andre
Dzeja, Petras
Kaambre, Tuuli
author_sort Klepinin, Aleksandr
collection PubMed
description Changes in dynamics of ATP γ- and β-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 γ- and β-ATP turnover in both breast cancer cells, compared to control. Lower β-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.
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spelling pubmed-91948142022-06-15 Stable Isotope Tracing Uncovers Reduced γ/β-ATP Turnover and Metabolic Flux Through Mitochondrial-Linked Phosphotransfer Circuits in Aggressive Breast Cancer Cells Klepinin, Aleksandr Miller, Sten Reile, Indrek Puurand, Marju Rebane-Klemm, Egle Klepinina, Ljudmila Vija, Heiki Zhang, Song Terzic, Andre Dzeja, Petras Kaambre, Tuuli Front Oncol Oncology Changes in dynamics of ATP γ- and β-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 γ- and β-ATP turnover in both breast cancer cells, compared to control. Lower β-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. Frontiers Media S.A. 2022-05-31 /pmc/articles/PMC9194814/ /pubmed/35712500 http://dx.doi.org/10.3389/fonc.2022.892195 Text en Copyright © 2022 Klepinin, Miller, Reile, Puurand, Rebane-Klemm, Klepinina, Vija, Zhang, Terzic, Dzeja and Kaambre https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Klepinin, Aleksandr
Miller, Sten
Reile, Indrek
Puurand, Marju
Rebane-Klemm, Egle
Klepinina, Ljudmila
Vija, Heiki
Zhang, Song
Terzic, Andre
Dzeja, Petras
Kaambre, Tuuli
Stable Isotope Tracing Uncovers Reduced γ/β-ATP Turnover and Metabolic Flux Through Mitochondrial-Linked Phosphotransfer Circuits in Aggressive Breast Cancer Cells
title Stable Isotope Tracing Uncovers Reduced γ/β-ATP Turnover and Metabolic Flux Through Mitochondrial-Linked Phosphotransfer Circuits in Aggressive Breast Cancer Cells
title_full Stable Isotope Tracing Uncovers Reduced γ/β-ATP Turnover and Metabolic Flux Through Mitochondrial-Linked Phosphotransfer Circuits in Aggressive Breast Cancer Cells
title_fullStr Stable Isotope Tracing Uncovers Reduced γ/β-ATP Turnover and Metabolic Flux Through Mitochondrial-Linked Phosphotransfer Circuits in Aggressive Breast Cancer Cells
title_full_unstemmed Stable Isotope Tracing Uncovers Reduced γ/β-ATP Turnover and Metabolic Flux Through Mitochondrial-Linked Phosphotransfer Circuits in Aggressive Breast Cancer Cells
title_short Stable Isotope Tracing Uncovers Reduced γ/β-ATP Turnover and Metabolic Flux Through Mitochondrial-Linked Phosphotransfer Circuits in Aggressive Breast Cancer Cells
title_sort stable isotope tracing uncovers reduced γ/β-atp turnover and metabolic flux through mitochondrial-linked phosphotransfer circuits in aggressive breast cancer cells
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194814/
https://www.ncbi.nlm.nih.gov/pubmed/35712500
http://dx.doi.org/10.3389/fonc.2022.892195
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