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Tumor Biology

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01.12.2012 | Research Article

ENTPD5-mediated modulation of ATP results in altered metabolism and decreased survival in gliomablastoma multiforme

verfasst von: Sohila Zadran, Arash Amighi, Erick Otiniano, Kaylee Wong, Homera Zadran

Erschienen in: Tumor Biology | Ausgabe 6/2012

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Abstract

Gliomablastoma multiforme (GBM) is the most aggressive of brain cancers in humans. Response to current therapies remains extremely poor, with dismal survival statistics. Recently, the endoplasmic reticulum UDPase, ectonucleoside triphosphate diphosphohydrolase 5 (ENTPD5), was identified as a key component in the Akt/phosphatidylinositol 3-kinase/phosphatase and tensin homolog regulatory loop, capable of synergizing aerobic glycolysis and cancer cell proliferation in vitro. Utilizing a novel enhanced acceptor fluorescence-based single-cell adenosine 5′-triphosphate (ATP) biosensor, we analyzed ENTPD5-mediated modulation of cytosolic ATP. Here, ENTPD5-dependent modulation of cellular ATP in GBM results in altered metabolic kinetics in vitro, increasing the catabolic efficiencies of aerobic glycolysis and fatty acid oxidation. Additionally, an upregulation of ENTPD5 in both GBM mouse xenografts and in GBM patient tumors was identified, resulting in dramatically reduced survival. Therefore, these results not only provide new tools to monitor ATP flux and cellular metabolism kinetics but also identified a novel therapeutic target for GBM.

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Titel: ENTPD5-mediated modulation of ATP results in altered metabolism and decreased survival in gliomablastoma multiforme
verfasst von: Sohila Zadran
Arash Amighi
Erick Otiniano
Kaylee Wong
Homera Zadran
Publikationsdatum: 01.12.2012
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 6/2012
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-012-0505-1

Springer Medizin

ENTPD5-mediated modulation of ATP results in altered metabolism and decreased survival in gliomablastoma multiforme

Abstract

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Springer Medizin

Abstract

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