CNR ExploRA

Articolo in rivista, 2023, ENG, 10.3390/ijms24044217

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

Chiara Cencioni 1, Fiorella Scagnoli 2, Francesco Spallotta 3,4 , Sergio Nasi 5, Barbara Illi 5

1. Institute of System Analysis and Informatics-National Research Council (IASI-CNR) 2. Axxam SpA 3. Department of Biology and Biotechnology Charles Darwin, Sapienza University 4. Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University 5. Institute of Molecular Biology and Pathology-National Research Council (IBPM-CNR)

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.

International journal of molecular sciences (Online)