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

Abstract:

: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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Janiszewska M,Suvà ML,Riggi N,Houtkooper RH,Auwerx J,Clément-Schatlo V,Radovanovic I,Rheinbay E,Provero P,Stamenkovic I

doi

10.1101/gad.188292.112

subject

Has Abstract

pub_date

2012-09-01 00:00:00

pages

1926-44

issue

17

eissn

0890-9369

issn

1549-5477

pii

gad.188292.112

journal_volume

26

pub_type

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