Kalkat Manpreet, De Melo Jason, Hickman Katherine Ashley, Lourenco Corey, Redel Cornelia, Resetca Diana, Tamachi Aaliya, Tu William B, Penn Linda Z
Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
Genes (Basel). 2017 May 25;8(6):151. doi: 10.3390/genes8060151.
MYC regulates a complex biological program by transcriptionally activating and repressing its numerous target genes. As such, MYC is a master regulator of many processes, including cell cycle entry, ribosome biogenesis, and metabolism. In cancer, the activity of the MYC transcriptional network is frequently deregulated, contributing to the initiation and maintenance of disease. Deregulation often leads to constitutive overexpression of MYC, which can be achieved through gross genetic abnormalities, including copy number alterations, chromosomal translocations, increased enhancer activity, or through aberrant signal transduction leading to increased transcription or increased MYC mRNA and protein stability. Herein, we summarize the frequency and modes of MYC deregulation and describe both well-established and more recent findings in a variety of cancer types. Notably, these studies have highlighted that with an increased appreciation for the basic mechanisms deregulating MYC in cancer, new therapeutic vulnerabilities can be discovered and potentially exploited for the inhibition of this potent oncogene in cancer.
MYC通过转录激活和抑制其众多靶基因来调控一个复杂的生物学程序。因此,MYC是许多过程的主要调节因子,包括细胞周期进入、核糖体生物发生和代谢。在癌症中,MYC转录网络的活性经常失调,这有助于疾病的起始和维持。失调通常导致MYC的组成型过表达,这可以通过严重的基因异常来实现,包括拷贝数改变、染色体易位、增强子活性增加,或通过异常信号转导导致转录增加或MYC mRNA和蛋白质稳定性增加。在此,我们总结了MYC失调的频率和模式,并描述了在多种癌症类型中已确立的和最新的发现。值得注意的是,这些研究强调,随着对癌症中MYC失调基本机制的认识不断增加,可以发现新的治疗靶点,并有可能利用这些靶点来抑制癌症中这种强大的致癌基因。