Ivano Amelio
TAp73 promotes anabolism
Amelio, Ivano; Antonov, Alexey A.; Catani, Maria Valeria; Massoud, Renato; Bernassola, Francesca; Knight, Richard A.; Melino, Gerry; Rufini, Alessandro
Authors
Alexey A. Antonov
Maria Valeria Catani
Renato Massoud
Francesca Bernassola
Richard A. Knight
Gerry Melino
Alessandro Rufini
Abstract
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.
Citation
Amelio, I., Antonov, A. A., Catani, M. V., Massoud, R., Bernassola, F., Knight, R. A., …Rufini, A. (2014). TAp73 promotes anabolism. Oncotarget, 5(24), 12820-12834. https://doi.org/10.18632/oncotarget.2667
Journal Article Type | Article |
---|---|
Acceptance Date | Oct 28, 2014 |
Online Publication Date | Nov 13, 2014 |
Publication Date | Dec 30, 2014 |
Deposit Date | Apr 1, 2020 |
Publicly Available Date | Apr 6, 2020 |
Journal | Oncotarget |
Publisher | Impact Journals |
Peer Reviewed | Peer Reviewed |
Volume | 5 |
Issue | 24 |
Pages | 12820-12834 |
DOI | https://doi.org/10.18632/oncotarget.2667 |
Public URL | https://nottingham-repository.worktribe.com/output/4236755 |
Publisher URL | https://www.oncotarget.com/article/2667/text/ |
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2667-35528-2-PB
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Publisher Licence URL
https://creativecommons.org/licenses/by/3.0/
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