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TAp73 is a marker o...
TAp73 is a marker of glutamine addiction in medulloblastoma
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- Niklison-Chirou, Maria Victoria (author)
- Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London E1 2AT, England.
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- Erngren, Ida (author)
- Uppsala universitet,Avdelningen för analytisk farmaceutisk kemi
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- Engskog, Mikael K R (author)
- Uppsala universitet,Avdelningen för analytisk farmaceutisk kemi
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- Haglöf, Jakob (author)
- Uppsala universitet,Avdelningen för analytisk farmaceutisk kemi
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- Picard, Daniel (author)
- Heinrich Heine Univ Dusseldorf, Dept Pediat Oncol Hematol & Clin Immunol, D-40225 Dusseldorf, Germany.;Heinrich Heine Univ Dusseldorf, Dept Neuropathol, Med Fac, D-40225 Dusseldorf, Germany.;German Canc Consortium DKTK, German Canc Res Ctr DKFZ, Dept Pediat Neurooncogen, D-69120 Heidelberg, Germany.
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- Remke, Marc (author)
- Heinrich Heine Univ Dusseldorf, Dept Pediat Oncol Hematol & Clin Immunol, D-40225 Dusseldorf, Germany.;Heinrich Heine Univ Dusseldorf, Dept Neuropathol, Med Fac, D-40225 Dusseldorf, Germany.;German Canc Consortium DKTK, German Canc Res Ctr DKFZ, Dept Pediat Neurooncogen, D-69120 Heidelberg, Germany.
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- McPolin, Phelim Hugh Redmond (author)
- Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London E1 2AT, England.
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- Selby, Matthew (author)
- Newcastle Univ, Wolfson Childhood Canc Res Ctr, Northern Inst Canc Res, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
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- Williamson, Daniel (author)
- Newcastle Univ, Wolfson Childhood Canc Res Ctr, Northern Inst Canc Res, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
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- Clifford, Steven C. (author)
- Newcastle Univ, Wolfson Childhood Canc Res Ctr, Northern Inst Canc Res, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
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- Michod, David (author)
- UCL, Inst Child Hlth, London WC1N 1EH, England.
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- Hadjiandreou, Michalis (author)
- Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London E1 2AT, England.
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- Arvidsson, Torbjörn (author)
- Uppsala universitet,Avdelningen för analytisk farmaceutisk kemi,Med Prod Agcy, SE-75103 Uppsala, Sweden.
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- Pettersson, Curt (author)
- Uppsala universitet,Avdelningen för analytisk farmaceutisk kemi
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- Melino, Gerry (author)
- Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England.
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- Marino, Silvia (author)
- Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London E1 2AT, England.
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Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London E1 2AT, England Avdelningen för analytisk farmaceutisk kemi (creator_code:org_t)
- 2017-09-26
- 2017
- English.
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In: Genes & Development. - : COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT. - 0890-9369 .- 1549-5477. ; 31:17, s. 1738-1753
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Abstract
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- 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.
Keyword
- medulloblastoma
- p73
- glutamine
- metabolomics
Publication and Content Type
- ref (subject category)
- art (subject category)
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Niklison-Chirou, ...
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Erngren, Ida
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Engskog, Mikael ...
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Haglöf, Jakob
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Picard, Daniel
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Remke, Marc
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McPolin, Phelim ...
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Selby, Matthew
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Williamson, Dani ...
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Clifford, Steven ...
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Michod, David
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Hadjiandreou, Mi ...
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Arvidsson, Torbj ...
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Pettersson, Curt
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Melino, Gerry
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Marino, Silvia
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Genes & Developm ...
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Uppsala University