Abstract：
MYC has been implicated in the pathogenesis of a wide range of human tumors and has been described for many years as a transcription factor that regulates genes with pleiotropic functions to promote tumorigenic growth. However, despite extensive efforts to identify specific target genes of MYC that alone could be responsible for promoting tumorigenesis, the field is yet to reach a consensus whether this is the crucial function of MYC. Recent work shifts the view on MYC\'s function from being a gene-specific transcription factor to an essential stress resilience factor. In highly proliferating cells, MYC preserves cell integrity by promoting DNA repair at core promoters, protecting stalled replication forks, and/or preventing transcription-replication conflicts. Furthermore, an increasing body of evidence demonstrates that MYC not only promotes tumorigenesis by driving cell-autonomous growth, but also enables tumors to evade the host\'s immune system. In this review, we summarize our current understanding of how MYC impairs antitumor immunity and why this function is evolutionarily hard-wired to the biology of the MYC protein family. We show why the cell-autonomous and immune evasive functions of MYC are mutually dependent and discuss ways to target MYC proteins in cancer therapy.
摘要：
MYC与多种人类肿瘤的发病机理有关，多年来一直被描述为一种转录因子，可调节具有多效性功能的基因以促进致瘤生长。然而,尽管在确定MYC的特定靶基因方面进行了大量努力，这些靶基因可能单独促进肿瘤发生，该领域尚未达成共识，这是否是MYC的关键功能。最近的工作将对MYC功能的看法从基因特异性转录因子转变为必需的应激复原因子。在高度增殖的细胞中，MYC通过促进核心启动子的DNA修复来保持细胞完整性，保护停滞的复制叉，和/或防止转录-复制冲突。此外，越来越多的证据表明，MYC不仅通过驱动细胞自主生长来促进肿瘤发生，还能使肿瘤逃避宿主的免疫系统。在这次审查中,我们总结了我们目前对MYC如何损害抗肿瘤免疫的理解，以及为什么这种功能在进化上与MYC蛋白家族的生物学联系在一起。我们展示了为什么MYC的细胞自主和免疫逃避功能是相互依赖的，并讨论了在癌症治疗中靶向MYC蛋白的方法。
