Department of Bioinformatics, Faculty of Medicine, Semmelweis University, 1094 Budapest, Hungary.
Institute of Enzymology, Research Centre for Natural Sciences, Eötvös Loránd Research Network, 1117 Budapest, Hungary.
Cells. 2023 Jun 29;12(13):1745. doi: 10.3390/cells12131745.
MYC is one of the most deregulated oncogenes on multiple levels in cancer. As a node transcription factor, MYC plays a diverse regulatory role in many cellular processes, including cell cycle and metabolism, both in physiological and pathological conditions. The relentless growth and proliferation of tumor cells lead to an insatiable demand for energy and nutrients, which requires the rewiring of cellular metabolism. As MYC can orchestrate all aspects of cellular metabolism, its altered regulation plays a central role in these processes, such as the Warburg effect, and is a well-established hallmark of cancer development. However, our current knowledge of MYC suggests that its spatial- and concentration-dependent contribution to tumorigenesis depends more on changes in the global or relative expression of target genes. As the direct targeting of MYC is proven to be challenging due to its relatively high toxicity, understanding its underlying regulatory mechanisms is essential for the development of tumor-selective targeted therapies. The aim of this review is to comprehensively summarize the diverse forms of MYC oncogenic deregulation, including DNA-, transcriptional- and post-translational level alterations, and their consequences for cellular metabolism. Furthermore, we also review the currently available and potentially attractive therapeutic options that exploit the vulnerability arising from the metabolic rearrangement of MYC-driven tumors.
MYC 是癌症中多个层面上最失调的癌基因之一。作为一个节点转录因子，MYC 在许多细胞过程中发挥着多样化的调节作用，包括细胞周期和代谢，无论是在生理还是病理条件下。肿瘤细胞的无休止生长和增殖导致对能量和营养的无止境需求，这需要对细胞代谢进行重新布线。由于 MYC 可以协调细胞代谢的各个方面，其改变的调节在这些过程中起着核心作用，例如沃伯格效应，并且是癌症发展的一个既定标志。然而，我们目前对 MYC 的了解表明，其对肿瘤发生的空间和浓度依赖性贡献更多地取决于靶基因的整体或相对表达的变化。由于直接针对 MYC 由于其相对较高的毒性而被证明具有挑战性，因此了解其潜在的调节机制对于开发肿瘤选择性靶向治疗至关重要。本综述的目的是全面总结 MYC 致癌失调的多种形式，包括 DNA、转录和翻译后水平的改变，以及它们对细胞代谢的影响。此外，我们还回顾了目前可用的和潜在有吸引力的治疗选择，这些选择利用了由 MYC 驱动的肿瘤代谢重排产生的脆弱性。
