Niklison-Chirou, MV;
Erngren, I;
Engskog, M;
Haglof, J;
Picard, D;
Remke, M;
McPolin, PHR;
... Marino, S; + view all
(2017)
TAp73 is a marker of glutamine addiction in medulloblastoma.
Genes & Development
, 31
(17)
pp. 1738-1753.
10.1101/gad.302349.117.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | TAp73 is a marker of glutamine addiction in medulloblastoma |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1101/gad.302349.117 |
| Publisher version: | http://dx.doi.org/10.1101/gad.302349.117 |
| Language: | English |
| Additional information: | © 2017 Niklison-Chirou et al.; Published by Cold Spring Harbor Laboratory Press 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/. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Cell Biology, Developmental Biology, Genetics & Heredity, Medulloblastoma, p73, Glutamine, Metabolomics, Cancer-Cells, Nutrient Deprivation, Regulates Autophagy, Oxidative Stress, Nervous-System, Metabolism, Mice, Survival, Defects |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10044031 |
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