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TAp73 is a marker of glutamine addiction in medulloblastoma

Medulloblastoma is the most common solid primary brain tumor in children. Remarkable advancements in the understanding of the genetic and epigenetic basis of these tumors have informed their recent molecular classification. However, the genotype/phenotype correlation of the subgroups remains largely...

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Autores principales: Niklison-Chirou, Maria Victoria, Erngren, Ida, Engskog, Mikael, Haglöf, Jakob, Picard, Daniel, Remke, Marc, McPolin, Phelim Hugh Redmond, Selby, Matthew, Williamson, Daniel, Clifford, Steven C., Michod, David, Hadjiandreou, Michalis, Arvidsson, Torbjörn, Pettersson, Curt, Melino, Gerry, Marino, Silvia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666673/
https://www.ncbi.nlm.nih.gov/pubmed/28971956
http://dx.doi.org/10.1101/gad.302349.117
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author Niklison-Chirou, Maria Victoria
Erngren, Ida
Engskog, Mikael
Haglöf, Jakob
Picard, Daniel
Remke, Marc
McPolin, Phelim Hugh Redmond
Selby, Matthew
Williamson, Daniel
Clifford, Steven C.
Michod, David
Hadjiandreou, Michalis
Arvidsson, Torbjörn
Pettersson, Curt
Melino, Gerry
Marino, Silvia
author_facet Niklison-Chirou, Maria Victoria
Erngren, Ida
Engskog, Mikael
Haglöf, Jakob
Picard, Daniel
Remke, Marc
McPolin, Phelim Hugh Redmond
Selby, Matthew
Williamson, Daniel
Clifford, Steven C.
Michod, David
Hadjiandreou, Michalis
Arvidsson, Torbjörn
Pettersson, Curt
Melino, Gerry
Marino, Silvia
author_sort Niklison-Chirou, Maria Victoria
collection PubMed
description Medulloblastoma is the most common solid primary brain tumor in children. Remarkable advancements in the understanding of the genetic and epigenetic basis of these tumors have informed their recent molecular classification. However, the genotype/phenotype correlation of the subgroups remains largely uncharacterized. In particular, the metabolic phenotype is of great interest because of its druggability, which could lead to the development of novel and more tailored therapies for a subset of medulloblastoma. p73 plays a critical role in a range of cellular metabolic processes. We show overexpression of p73 in a proportion of non-WNT medulloblastoma. In these tumors, p73 sustains cell growth and proliferation via regulation of glutamine metabolism. We validated our results in a xenograft model in which we observed an increase in survival time in mice on a glutamine restriction diet. Notably, glutamine starvation has a synergistic effect with cisplatin, a component of the current medulloblastoma chemotherapy. These findings raise the possibility that glutamine depletion can be used as an adjuvant treatment for p73-expressing medulloblastoma.
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spelling pubmed-56666732017-11-06 TAp73 is a marker of glutamine addiction in medulloblastoma Niklison-Chirou, Maria Victoria Erngren, Ida Engskog, Mikael Haglöf, Jakob Picard, Daniel Remke, Marc McPolin, Phelim Hugh Redmond Selby, Matthew Williamson, Daniel Clifford, Steven C. Michod, David Hadjiandreou, Michalis Arvidsson, Torbjörn Pettersson, Curt Melino, Gerry Marino, Silvia Genes Dev Research Paper Medulloblastoma is the most common solid primary brain tumor in children. Remarkable advancements in the understanding of the genetic and epigenetic basis of these tumors have informed their recent molecular classification. However, the genotype/phenotype correlation of the subgroups remains largely uncharacterized. In particular, the metabolic phenotype is of great interest because of its druggability, which could lead to the development of novel and more tailored therapies for a subset of medulloblastoma. p73 plays a critical role in a range of cellular metabolic processes. We show overexpression of p73 in a proportion of non-WNT medulloblastoma. In these tumors, p73 sustains cell growth and proliferation via regulation of glutamine metabolism. We validated our results in a xenograft model in which we observed an increase in survival time in mice on a glutamine restriction diet. Notably, glutamine starvation has a synergistic effect with cisplatin, a component of the current medulloblastoma chemotherapy. These findings raise the possibility that glutamine depletion can be used as an adjuvant treatment for p73-expressing medulloblastoma. Cold Spring Harbor Laboratory Press 2017-09-01 /pmc/articles/PMC5666673/ /pubmed/28971956 http://dx.doi.org/10.1101/gad.302349.117 Text en © 2017 Niklison-Chirou et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by/4.0/ This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Paper
Niklison-Chirou, Maria Victoria
Erngren, Ida
Engskog, Mikael
Haglöf, Jakob
Picard, Daniel
Remke, Marc
McPolin, Phelim Hugh Redmond
Selby, Matthew
Williamson, Daniel
Clifford, Steven C.
Michod, David
Hadjiandreou, Michalis
Arvidsson, Torbjörn
Pettersson, Curt
Melino, Gerry
Marino, Silvia
TAp73 is a marker of glutamine addiction in medulloblastoma
title TAp73 is a marker of glutamine addiction in medulloblastoma
title_full TAp73 is a marker of glutamine addiction in medulloblastoma
title_fullStr TAp73 is a marker of glutamine addiction in medulloblastoma
title_full_unstemmed TAp73 is a marker of glutamine addiction in medulloblastoma
title_short TAp73 is a marker of glutamine addiction in medulloblastoma
title_sort tap73 is a marker of glutamine addiction in medulloblastoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666673/
https://www.ncbi.nlm.nih.gov/pubmed/28971956
http://dx.doi.org/10.1101/gad.302349.117
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