Metabolic effect of TAp63α : enhanced glycolysis and pentose phosphate pathway, resulting in increased antioxidant defense

D'Alessandro, Angelo; Amelio, Ivano; Berkers, Celia R.; Antonov, Alexey; Vousden, Karen H.; Melino, Gerry; Zolla, Lello

Metabolic effect of TAp63α : enhanced glycolysis and pentose phosphate pathway, resulting in increased antioxidant defense

Dateien

D'Alessandro_2-tybb5ihnq0qf4.pdfGröße: 1.43 MBDownloads: 30

Datum

2014

Autor:innen

D'Alessandro, Angelo

Amelio, Ivano

Berkers, Celia R.

Antonov, Alexey

Vousden, Karen H.

Melino, Gerry

Zolla, Lello

Open Access-Veröffentlichung

Open Access Gold

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Oncotarget. Impact Journals LLC. 2014, 5(17), pp. 7722-7733. eISSN 1949-2553. Available under: doi: 10.18632/oncotarget.2300

Zusammenfassung

TAp63α is a member of the p53 family, which plays a central role in epithelial cancers. Recently, a role has emerged for p53 family members in cancer metabolic modulation. In order to assess whether TAp63α plays a role in cancer metabolism, we exploited p53-null osteosarcoma Tet-On Saos-2 cells, in which the expression of TAp63α was dependent on doxycycline supplementation to the medium. Metabolomics labeling experiments were performed by incubating the cells in ¹³C-glucose or ¹³C¹⁵N-glutamine-labeled culture media, as to monitor metabolic fluxes upon induced expression of TAp63α. Induced expression of TAp63α resulted in cell cycle arrest at the G1 phase. From a metabolic standpoint, expression of Tap63α promoted glycolysis and the pentose phosphate pathway, which was uncoupled from nucleotide biosynthesis, albeit prevented oxidative stress in the form of oxidized glutathione. Double 13C-glucose and 13C15N-glutamine metabolic labeling confirmed that induced expression of TAp63α corresponded to a decreased flux of pyruvate to the Krebs cycle and decreased utilization of glutamine for catabolic purposes in the TCA cycle. Results were not conclusive in relation to anabolic utilization of labeled glutamine, since it is unclear to what extent the observed minor TAp63α-dependent increases of glutamine-derived labeling in palmitate could be tied to increased rates of reductive carboxylation and de novo synthesis of fatty acids. Finally, bioinformatics elaborations highlighted a link between patient survival rates and the co-expression of p63 and rate limiting enzymes of the pentose phosphate pathway, G6PD and PGD.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Schlagwörter

p63, p53 family, metabolomics, glycolysis, glutaminolysis

Zitieren

ISO 690

D'ALESSANDRO, Angelo, Ivano AMELIO, Celia R. BERKERS, Alexey ANTONOV, Karen H. VOUSDEN, Gerry MELINO, Lello ZOLLA, 2014. Metabolic effect of TAp63α : enhanced glycolysis and pentose phosphate pathway, resulting in increased antioxidant defense. In: Oncotarget. Impact Journals LLC. 2014, 5(17), pp. 7722-7733. eISSN 1949-2553. Available under: doi: 10.18632/oncotarget.2300

BibTex

@article{DAlessandro2014Metab-57088,
  year={2014},
  doi={10.18632/oncotarget.2300},
  title={Metabolic effect of TAp63α : enhanced glycolysis and pentose phosphate pathway, resulting in increased antioxidant defense},
  number={17},
  volume={5},
  journal={Oncotarget},
  pages={7722--7733},
  author={D'Alessandro, Angelo and Amelio, Ivano and Berkers, Celia R. and Antonov, Alexey and Vousden, Karen H. and Melino, Gerry and Zolla, Lello}
}

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