State Key Laboratory of Oncology in South China, Collaborative Innovation center for Cancer Medicine, Sun Yat-sen University cancer center, Guangzhou, Guangdong, China; Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong, China.
Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Digestive diseases, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Pharmacol Res. 2019 Nov;149:104352. doi: 10.1016/j.phrs.2019.104352. Epub 2019 Jul 16.
Mammalian / mechanistic target of rapamycin (mTOR) is a critical sensor of environmental cues that regulates cellular macromolecule synthesis and metabolism in eukaryotes. DNA methylation is the most well-studied epigenetic modification that is capable of regulating gene transcription and affecting genome stability. Both dysregulation of mTOR signaling and DNA methylation patterns have been shown to be closely linked to tumor progression and serve as promising targets for cancer therapy. Although their respective roles in tumorigenesis have been extensively studied, whether molecular interplay exists between them is still largely unknown. In this review, we provide a brief overview of mTOR signaling, DNA methylation as well as related serine and one-carbon metabolism, one of the most critical aspects of metabolic reprogramming in cancer. Based on the latest understanding regarding the regulation of metabolic processes by mTOR signaling as well as interaction between metabolism and epigenetics, we further discuss how serine and one-carbon metabolism may serve as a bridge that links mTOR signaling and DNA methylation to promote tumor growth. Elucidating their relationship may provide novel insight for cancer therapy in the future.
哺乳动物/雷帕霉素靶蛋白（mTOR）是一种环境信号的关键传感器，它在真核生物中调节细胞大分子的合成和代谢。DNA 甲基化是研究最广泛的表观遗传修饰之一，能够调节基因转录并影响基因组稳定性。mTOR 信号的失调和 DNA 甲基化模式的失调都与肿瘤的进展密切相关，是癌症治疗的有前途的靶点。尽管它们在肿瘤发生中的各自作用已经得到了广泛的研究，但它们之间是否存在分子相互作用在很大程度上仍然未知。在这篇综述中，我们简要概述了 mTOR 信号、DNA 甲基化以及相关的丝氨酸和一碳代谢，这是癌症代谢重编程中最关键的方面之一。基于最新的关于 mTOR 信号对代谢过程的调节以及代谢和表观遗传学之间的相互作用的理解，我们进一步讨论了丝氨酸和一碳代谢如何作为连接 mTOR 信号和 DNA 甲基化以促进肿瘤生长的桥梁。阐明它们之间的关系可能为未来的癌症治疗提供新的见解。
