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TAp73 is a marker of glutamine addiction in medulloblastoma

Lookup NU author(s): Dr Matthew Selby, Dr Daniel Williamson, Professor Steven Clifford

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2017 Niklison-Chirou et al. 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 xeno-graft 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.


Publication metadata

Author(s): Niklison-Chirou MV, Erngren I, Engskog M, Haglof J, Picard D, Remke M, McPolin PHR, Selby M, Williamson D, Clifford SC, Michod D, Hadjiandreou M, Arvidsson T, Pettersson C, Melino G, Marino S

Publication type: Article

Publication status: Published

Journal: Genes and Development

Year: 2017

Volume: 31

Issue: 17

Pages: 1738-1753

Print publication date: 01/09/2017

Online publication date: 26/09/2017

Acceptance date: 05/09/2017

Date deposited: 07/12/2017

ISSN (print): 0890-9369

ISSN (electronic): 1549-5477

Publisher: Cold Spring Harbor Laboratory Press

URL: https://doi.org/10.1101/gad.302349.117

DOI: 10.1101/gad.302349.117


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