Imp2 controls oxidative phosphorylation and is crucial for preserving glioblastoma cancer stem cells.

Détails

Ressource 1Télécharger: PMID22899010.pdf (1996.79 [Ko])
Etat: Serval
Version: Final published version
ID Serval
serval:BIB_82549B173DDD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Imp2 controls oxidative phosphorylation and is crucial for preserving glioblastoma cancer stem cells.
Périodique
Genes and Development
Auteur(s)
Janiszewska M., Suvà M.L., Riggi N., Houtkooper R.H., Auwerx J., Clément-Schatlo V., Radovanovic I., Rheinbay E., Provero P., Stamenkovic I.
ISSN
1549-5477 (Electronic)
ISSN-L
0890-9369
Statut éditorial
Publié
Date de publication
10/2012
Peer-reviewed
Oui
Volume
26
Numéro
17
Pages
1926-1944
Langue
anglais
Résumé
Growth of numerous cancer types is believed to be driven by a subpopulation of poorly differentiated cells, often referred to as cancer stem cells (CSCs), that have the capacity for self-renewal, tumor initiation, and generation of nontumorigenic progeny. Despite their potentially key role in tumor establishment and maintenance, the energy requirements of these cells and the mechanisms that regulate their energy production are unknown. Here, we show that the oncofetal insulin-like growth factor 2 mRNA-binding protein 2 (IMP2, IGF2BP2) regulates oxidative phosphorylation (OXPHOS) in primary glioblastoma (GBM) sphere cultures (gliomaspheres), an established in vitro model for CSC expansion. We demonstrate that IMP2 binds several mRNAs that encode mitochondrial respiratory chain complex subunits and that it interacts with complex I (NADH:ubiquinone oxidoreductase) proteins. Depletion of IMP2 in gliomaspheres decreases their oxygen consumption rate and both complex I and complex IV activity that results in impaired clonogenicity in vitro and tumorigenicity in vivo. Importantly, inhibition of OXPHOS but not of glycolysis abolishes GBM cell clonogenicity. Our observations suggest that gliomaspheres depend on OXPHOS for their energy production and survival and that IMP2 expression provides a key mechanism to ensure OXPHOS maintenance by delivering respiratory chain subunit-encoding mRNAs to mitochondria and contributing to complex I and complex IV assembly.
Mots-clé
Imp2, Cancer stem cells, OXPHOS, Glioblastoma, Respiratory complex, Mitochondria
Pubmed
Web of science
Open Access
Oui
Création de la notice
27/09/2012 19:11
Dernière modification de la notice
08/05/2019 21:12
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