Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783275349306507264 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5666673 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT niklisonchiroumariavictoria tap73isamarkerofglutamineaddictioninmedulloblastoma AT erngrenida tap73isamarkerofglutamineaddictioninmedulloblastoma AT engskogmikael tap73isamarkerofglutamineaddictioninmedulloblastoma AT haglofjakob tap73isamarkerofglutamineaddictioninmedulloblastoma AT picarddaniel tap73isamarkerofglutamineaddictioninmedulloblastoma AT remkemarc tap73isamarkerofglutamineaddictioninmedulloblastoma AT mcpolinphelimhughredmond tap73isamarkerofglutamineaddictioninmedulloblastoma AT selbymatthew tap73isamarkerofglutamineaddictioninmedulloblastoma AT williamsondaniel tap73isamarkerofglutamineaddictioninmedulloblastoma AT cliffordstevenc tap73isamarkerofglutamineaddictioninmedulloblastoma AT michoddavid tap73isamarkerofglutamineaddictioninmedulloblastoma AT hadjiandreoumichalis tap73isamarkerofglutamineaddictioninmedulloblastoma AT arvidssontorbjorn tap73isamarkerofglutamineaddictioninmedulloblastoma AT petterssoncurt tap73isamarkerofglutamineaddictioninmedulloblastoma AT melinogerry tap73isamarkerofglutamineaddictioninmedulloblastoma AT marinosilvia tap73isamarkerofglutamineaddictioninmedulloblastoma |