Institute of System Analysis and Informatics-National Research Council (IASI-CNR), 00185 Rome, Italy.
Axxam SpA, Bresso, 20091 Milan, Italy.
Int J Mol Sci. 2023 Feb 20;24(4):4217. doi: 10.3390/ijms24044217.
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.
过去几年中，Myc（c-myc、n-myc、l-myc）癌基因作为一种典型的 DNA 结合转录因子的概念不断发生变化。事实上，Myc 在多个层面上控制基因表达程序：直接结合染色质并招募转录共激活因子；调节 RNA 聚合酶（RNAP）的活性；并绘制染色质拓扑结构。因此，Myc 在癌症中的失调显然是一个戏剧性的事件。多形性胶质母细胞瘤（GBM）是成人中最致命、仍然无法治愈的脑癌，在大多数情况下，其特征是 Myc 失调。代谢重编程通常发生在癌细胞中，而 GBM 经历深刻的代谢变化以供应增加的能量需求。在非转化细胞中，Myc 严格控制代谢途径以维持细胞内稳态。一致地，在 Myc 过表达的癌细胞中，包括 GBM 细胞，这些高度受控的代谢途径受到增强的 Myc 活性的影响，并显示出实质性的改变。另一方面，失调的癌症代谢会影响 Myc 的表达和功能，使 Myc 处于代谢途径激活和基因表达的交汇点。在这篇综述文章中，我们总结了有关 GBM 代谢的现有信息，特别关注 Myc 癌基因的控制，反过来，Myc 又控制代谢信号的激活，以确保 GBM 的生长。
