Titre
MYCN-enhanced Oxidative and Glycolytic Metabolism Reveals Vulnerabilities for Targeting Neuroblastoma.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Oliynyk, G.
Co-première auteure/Co-premier auteur
Ruiz-Pérez, M.V.
Co-première auteure/Co-premier auteur
Sainero-Alcolado, L.
Auteure/Auteur
Dzieran, J.
Auteure/Auteur
Zirath, H.
Auteure/Auteur
Gallart-Ayala, H.
Auteure/Auteur
Wheelock, C.E.
Auteure/Auteur
Johansson, H.J.
Auteure/Auteur
Nilsson, R.
Auteure/Auteur
Lehtiö, J.
Auteure/Auteur
Arsenian-Henriksson, M.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
2589-0042
Statut éditorial
Publié
Date de publication
2019-11-22
Volume
21
Première page
188
Dernière page/numéro d’article
204
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
In pediatric neuroblastoma, MYCN-amplification correlates to poor clinical outcome and new treatment options are needed for these patients. Identifying the metabolic adaptations crucial for tumor progression may be a promising strategy to discover novel therapeutic targets. Here, we have combined proteomics, gene expression profiling, functional analysis, and metabolic tracing to decipher the impact of MYCN on neuroblastoma cell metabolism. We found that high MYCN levels are correlated with altered expression of proteins involved in multiple metabolic processes, including enhanced glycolysis and increased oxidative phosphorylation. Unexpectedly, we discovered that MYCN-amplified cells showed de novo glutamine synthesis. Furthermore, inhibition of β-oxidation reduced the viability of MYCN-amplified cells in vitro and decreased tumor burden in vivo, while not affecting non-MYCN-amplified tumors. Our data provide information on metabolic processes in MYCN expressing tumors, which could be exploited for the development of novel targeted therapies.
PID Serval
serval:BIB_0B4B913E7856
PMID
Open Access
Oui
Date de création
2019-11-02T21:57:38.924Z
Date de création dans IRIS
2025-05-20T19:11:51Z
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Nom
31670074_BIB_0B4B913E7856.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by-nc-nd/4.0
Taille
16.37 MB
Format
Adobe PDF
PID Serval
serval:BIB_0B4B913E7856.P001
URN
urn:nbn:ch:serval-BIB_0B4B913E78566
Somme de contrôle
(MD5):bfaef851bd0263693f180647df0f0268