Open Close
Reference
Citation
Bonnay, F., Veloso, A., Steinmann, V., Köcher, T., Abdusselamoglu, M.D., Bajaj, S., Rivelles, E., Landskron, L., Esterbauer, H., Zinzen, R.P., Knoblich, J.A. (2020). Oxidative Metabolism Drives Immortalization of Neural Stem Cells during Tumorigenesis.  Cell 182(6): 1490--1507.e19.
FlyBase ID
FBrf0246717
Publication Type
Research paper
Abstract

Metabolic reprogramming is a key feature of many cancers, but how and when it contributes to tumorigenesis remains unclear. Here we demonstrate that metabolic reprogramming induced by mitochondrial fusion can be rate-limiting for immortalization of tumor-initiating cells (TICs) and trigger their irreversible dedication to tumorigenesis. Using single-cell transcriptomics, we find that Drosophila brain tumors contain a rapidly dividing stem cell population defined by upregulation of oxidative phosphorylation (OxPhos). We combine targeted metabolomics and in vivo genetic screening to demonstrate that OxPhos is required for tumor cell immortalization but dispensable in neural stem cells (NSCs) giving rise to tumors. Employing an in vivo NADH/NAD+ sensor, we show that NSCs precisely increase OxPhos during immortalization. Blocking OxPhos or mitochondrial fusion stalls TICs in quiescence and prevents tumorigenesis through impaired NAD+ regeneration. Our work establishes a unique connection between cellular metabolism and immortalization of tumor-initiating cells.

PubMed ID
PubMed Central ID
Associated Information
Comments
Associated Files
File date: 2020.10.5 ; File size: 2988 ; File format: tsv ; File name: FBrf0246717.FTYP.2020.10.5.tsv
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell
    Title
    Cell
    Publication Year
    1974-
    ISBN/ISSN
    0092-8674
    Data From Reference
    Alleles (52)
    Genes (41)
    Natural transposons (1)
    Insertions (1)
    Experimental Tools (5)
    Transgenic Constructs (51)