TAp73 promotes anabolism

Amelio, Ivano; Antonov, Alexey A.; Catani, Maria Valeria; Massoud, Renato; Bernassola, Francesca; Knight, Richard A.; Melino, Gerry; Rufini, Alessandro

TAp73 promotes anabolism

Dateien

Zu diesem Dokument gibt es keine Dateien.

Datum

2014

Autor:innen

Amelio, Ivano

Antonov, Alexey A.

Catani, Maria Valeria

Massoud, Renato

Bernassola, Francesca

Knight, Richard A.

Melino, Gerry

Rufini, Alessandro

DOI (zitierfähiger Link)

https://doi.org/10.18632/oncotarget.2667

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Oncotarget. Impact Journals LLC. 2014, 5(24), pp. 12820-12834. eISSN 1949-2553. Available under: doi: 10.18632/oncotarget.2667

Zusammenfassung

Metabolic adaptation has emerged as a hallmark of cancer and a promising therapeutic target, as rapidly proliferating cancer cells adapt their metabolism increasing nutrient uptake and reorganizing metabolic fluxes to support biosynthesis. The transcription factor p73 belongs to the p53-family and regulates tumorigenesis via its two N-terminal isoforms, with (TAp73) or without (ΔNp73) a transactivation domain. TAp73 acts as tumor suppressor, at least partially through induction of cell cycle arrest and apoptosis and through regulation of genomic stability. Here, we sought to investigate whether TAp73 also affects metabolic profiling of cancer cells. Using high throughput metabolomics, we unveil a thorough and unexpected role for TAp73 in promoting Warburg effect and cellular metabolism. TAp73-expressing cells show increased rate of glycolysis, higher amino acid uptake and increased levels and biosynthesis of acetyl-CoA. Moreover, we report an extensive TAp73-mediated upregulation of several anabolic pathways including polyamine and synthesis of membrane phospholipids. TAp73 expression also increases cellular methyl-donor S-adenosylmethionine (SAM), possibly influencing methylation and epigenetics, and promotes arginine metabolism, suggestive of a role in extracellular matrix (ECM) modeling. In summary, our data indicate that TAp73 regulates multiple metabolic pathways that impinge on numerous cellular functions, but that, overall, converge to sustain cell growth and proliferation.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Schlagwörter

p73, p53, Metabolism, Warburg effect, cancer

Zitieren

ISO 690

AMELIO, Ivano, Alexey A. ANTONOV, Maria Valeria CATANI, Renato MASSOUD, Francesca BERNASSOLA, Richard A. KNIGHT, Gerry MELINO, Alessandro RUFINI, 2014. TAp73 promotes anabolism. In: Oncotarget. Impact Journals LLC. 2014, 5(24), pp. 12820-12834. eISSN 1949-2553. Available under: doi: 10.18632/oncotarget.2667

BibTex

@article{Amelio2014-12-30TAp73-57081,
  year={2014},
  doi={10.18632/oncotarget.2667},
  title={TAp73 promotes anabolism},
  number={24},
  volume={5},
  journal={Oncotarget},
  pages={12820--12834},
  author={Amelio, Ivano and Antonov, Alexey A. and Catani, Maria Valeria and Massoud, Renato and Bernassola, Francesca and Knight, Richard A. and Melino, Gerry and Rufini, Alessandro}
}

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    <dcterms:abstract xml:lang="eng">Metabolic adaptation has emerged as a hallmark of cancer and a promising therapeutic target, as rapidly proliferating cancer cells adapt their metabolism increasing nutrient uptake and reorganizing metabolic fluxes to support biosynthesis. The transcription factor p73 belongs to the p53-family and regulates tumorigenesis via its two N-terminal isoforms, with (TAp73) or without (ΔNp73) a transactivation domain. TAp73 acts as tumor suppressor, at least partially through induction of cell cycle arrest and apoptosis and through regulation of genomic stability. Here, we sought to investigate whether TAp73 also affects metabolic profiling of cancer cells. Using high throughput metabolomics, we unveil a thorough and unexpected role for TAp73 in promoting Warburg effect and cellular metabolism. TAp73-expressing cells show increased rate of glycolysis, higher amino acid uptake and increased levels and biosynthesis of acetyl-CoA. Moreover, we report an extensive TAp73-mediated upregulation of several anabolic pathways including polyamine and synthesis of membrane phospholipids. TAp73 expression also increases cellular methyl-donor S-adenosylmethionine (SAM), possibly influencing methylation and epigenetics, and promotes arginine metabolism, suggestive of a role in extracellular matrix (ECM) modeling. In summary, our data indicate that TAp73 regulates multiple metabolic pathways that impinge on numerous cellular functions, but that, overall, converge to sustain cell growth and proliferation.</dcterms:abstract>
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