c-MYC inhibition impairs hypoxia response in glioblastoma multiforme

M. P. Mongiardi, Mauro Savino, Maria Laura Falchetti, Barbara Illi, Francesca Bozzo, Cristiana Valle, Manuela Helmer-Citterich, Fabrizio Ferrè, Sergio Nasi, Andrea Levi

Research output: Contribution to journalArticlepeer-review

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 hypoxiadependent 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.

Original languageEnglish
Pages (from-to)33257-33271
Number of pages15
JournalOncotarget
Volume7
Issue number22
DOIs
Publication statusPublished - May 31 2016

Keywords

  • c-MYC
  • Glioblastoma
  • Glycolysis
  • HIF
  • Hypoxia

ASJC Scopus subject areas

  • Oncology

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