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  • Title: c-MYC inhibition impairs hypoxia response in glioblastoma multiforme.
    Author: Mongiardi MP, Savino M, Falchetti ML, Illi B, Bozzo F, Valle C, Helmer-Citterich M, Ferrè F, Nasi S, Levi A.
    Journal: Oncotarget; 2016 May 31; 7(22):33257-71. PubMed ID: 27119353.
    Abstract:
    The c-MYC oncoprotein is a DNA binding transcription factor that enhances the expression of many active genes. c-MYC transcriptional signatures vary according to the transcriptional program defined in each cell type during differentiation. Little is known on the involvement of c-MYC in regulation of gene expression programs that are induced by extracellular cues such as a changing microenvironment. Here we demonstrate that inhibition of c-MYC in glioblastoma multiforme cells blunts hypoxia-dependent glycolytic reprogramming and mitochondria fragmentation in hypoxia. This happens because c-MYC inhibition alters the cell transcriptional response to hypoxia and finely tunes the expression of a subset of Hypoxia Inducible Factor 1-regulated genes. We also show that genes whose expression in hypoxia is affected by c-MYC inhibition are able to distinguish the Proneural subtype of glioblastoma multiforme, thus potentially providing a molecular signature for this class of tumors that are the least tractable among glioblastomas.
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