The "Superoncogene" Myc at the Crossroad between Metabolism and Gene Expression in Glioblastoma Multiforme

Int J Mol Sci. 2023 Feb 20;24(4):4217. doi: 10.3390/ijms24044217.

Abstract

The concept of the Myc (c-myc, n-myc, l-myc) oncogene as a canonical, DNA-bound transcription factor has consistently changed over the past few years. Indeed, Myc controls gene expression programs at multiple levels: directly binding chromatin and recruiting transcriptional coregulators; modulating the activity of RNA polymerases (RNAPs); and drawing chromatin topology. Therefore, it is evident that Myc deregulation in cancer is a dramatic event. Glioblastoma multiforme (GBM) is the most lethal, still incurable, brain cancer in adults, and it is characterized in most cases by Myc deregulation. Metabolic rewiring typically occurs in cancer cells, and GBM undergoes profound metabolic changes to supply increased energy demand. In nontransformed cells, Myc tightly controls metabolic pathways to maintain cellular homeostasis. Consistently, in Myc-overexpressing cancer cells, including GBM cells, these highly controlled metabolic routes are affected by enhanced Myc activity and show substantial alterations. On the other hand, deregulated cancer metabolism impacts Myc expression and function, placing Myc at the intersection between metabolic pathway activation and gene expression. In this review paper, we summarize the available information on GBM metabolism with a specific focus on the control of the Myc oncogene that, in turn, rules the activation of metabolic signals, ensuring GBM growth.

Keywords: Myc; gene expression; glioblastoma; metabolic control.

Publication types

  • Review

MeSH terms

  • Adult
  • Brain Neoplasms* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Chromatin
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma* / metabolism
  • Humans
  • Proto-Oncogene Proteins c-myc / metabolism

Substances

  • Proto-Oncogene Proteins c-myc
  • Chromatin

Grants and funding

This work was supported by AIRC (Italian Association for Cancer Research); MFAG grant number 23099 to Francesco Spallotta.