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

The concept of the Myc (c-myc, n-myc, l-myc) oncogene as a canonical, DNA-boundtranscription factor has consistently changed over the past few years. Indeed, Myc controls geneexpression programs at multiple levels: directly binding chromatin and recruiting transcriptionalcoregulators; 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 mostcases by Myc deregulation. Metabolic rewiring typically occurs in cancer cells, and GBM undergoesprofound metabolic changes to supply increased energy demand. In nontransformed cells, Myc tightlycontrols metabolic pathways to maintain cellular homeostasis. Consistently, in Myc-overexpressingcancer cells, including GBM cells, these highly controlled metabolic routes are affected by enhancedMyc activity and show substantial alterations. On the other hand, deregulated cancer metabolismimpacts Myc expression and function, placing Myc at the intersection between metabolic pathwayactivation and gene expression. In this review paper, we summarize the available information onGBM metabolism with a specific focus on the control of the Myc oncogene that, in turn, rules theactivation of metabolic signals, ensuring GBM growth.