TAp73 is a marker of glutamine addiction in medulloblastoma

Maria Victoria Niklison-Chirou, Ida Erngren, Mikael Engskog, Jakob Haglöf, Daniel Picard, Marc Remke, Phelim Hugh Redmond McPolin, Matthew Selby, Daniel Williamson, Steven C. Clifford, David Michod, Michalis Hadjiandreou, Torbjörn Arvidsson, Curt Pettersson, Gerry Melino, Silvia Marino

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19 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)1738-1753
Number of pages16
JournalGenes and Development
Volume31
Issue number17
DOIs
Publication statusPublished - 1 Sep 2017

Keywords

  • Glutamine
  • Medulloblastoma
  • Metabolomics
  • P73

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Niklison-Chirou, M. V., Erngren, I., Engskog, M., Haglöf, J., Picard, D., Remke, M., McPolin, P. H. R., Selby, M., Williamson, D., Clifford, S. C., Michod, D., Hadjiandreou, M., Arvidsson, T., Pettersson, C., Melino, G., & Marino, S. (2017). TAp73 is a marker of glutamine addiction in medulloblastoma. Genes and Development, 31(17), 1738-1753. https://doi.org/10.1101/gad.302349.117