Department of Biochemistry and Molecular Biology A, University of Murcia, Murcia, Spain.
Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
Oncogene. 2015 Jan 8;34(2):135-43. doi: 10.1038/onc.2013.605. Epub 2014 Jan 27.
Cancer is characterized by uncontrolled cell growth and the acquisition of metastatic properties. In most cases, the activation of oncogenes and/or deactivation of tumour suppressor genes lead to uncontrolled cell cycle progression and inactivation of apoptotic mechanisms. Although the underlying mechanisms of carcinogenesis remain unknown, increasing evidence links aberrant regulation of methylation to tumourigenesis. In addition to the methylation of DNA and histones, methylation of nonhistone proteins, such as transcription factors, is also implicated in the biology and development of cancer. Because the metabolic cycling of methionine is a key pathway for many of these methylating reactions, strategies to target the epigenetic machinery of cancer cells could result in novel and efficient anticancer therapies. The application of these new epigenetic therapies could be of utility in the promotion of E2F1-dependent apoptosis in cancer cells, in avoiding metastatic pathways and/or in sensitizing tumour cells to radiotherapy.
癌症的特征是细胞不受控制地生长，并获得转移特性。在大多数情况下，癌基因的激活和/或肿瘤抑制基因的失活导致细胞周期失控和凋亡机制失活。尽管致癌作用的潜在机制尚不清楚，但越来越多的证据表明，甲基化的异常调节与肿瘤发生有关。除了 DNA 和组蛋白的甲基化外，转录因子等非组蛋白的甲基化也与癌症的生物学和发展有关。由于甲硫氨酸的代谢循环是许多这些甲基化反应的关键途径，因此针对癌细胞表观遗传机制的策略可能会产生新的、有效的抗癌疗法。这些新的表观遗传学疗法的应用可能有助于促进癌细胞中 E2F1 依赖性凋亡，避免转移途径，或使肿瘤细胞对放疗敏感。
