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Parkinson, E.K.* ; Adamski, J. ; Zahn, G.* ; Gaumann, A.* ; Flores-Borja, F.* ; Ziegler, C.* ; Mycielska, M.E.*

Extracellular citrate and metabolic adaptations of cancer cells.

Cancer Metastasis Rev., DOI: 10.1007/s10555-021-10007-1 (2021)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
It is well established that cancer cells acquire energy via the Warburg effect and oxidative phosphorylation. Citrate is considered to play a crucial role in cancer metabolism by virtue of its production in the reverse Krebs cycle from glutamine. Here, we review the evidence that extracellular citrate is one of the key metabolites of the metabolic pathways present in cancer cells. We review the different mechanisms by which pathways involved in keeping redox balance respond to the need of intracellular citrate synthesis under different extracellular metabolic conditions. In this context, we further discuss the hypothesis that extracellular citrate plays a role in switching between oxidative phosphorylation and the Warburg effect while citrate uptake enhances metastatic activities and therapy resistance. We also present the possibility that organs rich in citrate such as the liver, brain and bones might form a perfect niche for the secondary tumour growth and improve survival of colonising cancer cells. Consistently, metabolic support provided by cancer-associated and senescent cells is also discussed. Finally, we highlight evidence on the role of citrate on immune cells and its potential to modulate the biological functions of pro- and anti-tumour immune cells in the tumour microenvironment. Collectively, we review intriguing evidence supporting the potential role of extracellular citrate in the regulation of the overall cancer metabolism and metastatic activity.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Korrespondenzautor
Schlagwörter Cancer-associated Cells ; Citrate ; Oxphos ; Redox ; Senescence ; Warburg Effect; Pentose-phosphate Pathway; Malic Enzyme; Plasma Citrate; Oxidative Stress; Tumor Microenvironment; Lactate-dehydrogenase; Malate-dehydrogenase; Citric-acid; Dna-damage; Tca Cycle
ISSN (print) / ISBN 0167-7659
e-ISSN 1573-7233
Zeitschrift Cancer and Metastasis Reviews
Verlag Springer
Verlagsort Dordrecht, Netherlands
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Experimental Genetics (IEG)
Förderungen Deutsche Forschungsgemeinschaft