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TAp73 is a marker of glutamine addiction in medulloblastoma
Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London E1 2AT, England..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.ORCID iD: 0000-0001-8650-6245
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2017 (English)In: Genes & Development, ISSN 0890-9369, E-ISSN 1549-5477, Vol. 31, no 17, p. 1738-1753Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT , 2017. Vol. 31, no 17, p. 1738-1753
Keywords [en]
medulloblastoma, p73, glutamine, metabolomics
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-336829DOI: 10.1101/gad.302349.117ISI: 000412275500004PubMedID: 28971956OAI: oai:DiVA.org:uu-336829DiVA, id: diva2:1168123
Available from: 2017-12-20 Created: 2017-12-20 Last updated: 2017-12-20Bibliographically approved

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Erngren, IdaEngskog, Mikael K RHaglöf, JakobArvidsson, TorbjörnPettersson, Curt
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