Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, USA; Division of Oncology, Department of Internal Medicine, USA; Cancer Biology Program, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Pharmacol Ther. 2015 Jun;150:33-46. doi: 10.1016/j.pharmthera.2015.01.004. Epub 2015 Jan 13.
The epithelial-mesenchymal transition (EMT) is a developmental process that is important for embryogenesis, wound healing, organ fibrosis, and cancer metastasis. Cancer-associated EMT is not a simple process to acquire migration and invasion ability, but a complicated and comprehensive reprogramming, involved in metabolism, epigenetics and differentiation, through which differentiated epithelial cancer cells reverse to an undifferentiated state, not only expressing stem cell markers, but also acquiring stem cell-like functions. Here we review recent ideas and discoveries that illustrate the links among metabolism, epigenetics, and dedifferentiation during EMT, with special emphasis on the primary driving force and ultimate goal of cancer-associated EMT - of the energy and for the energy. Furthermore, we highlight on the specificity of epigenetic modification during EMT, with an aim to explain how the repression of epithelial genes and activation of mesenchymal genes are coordinated simultaneously through EMT. Finally, we provide an outlook on anti-EMT therapeutic approach on epigenetic and metabolic levels, and discuss its potential for clinical application.
上皮-间充质转化(EMT)是一个对于胚胎发生、创伤愈合、器官纤维化和癌症转移都非常重要的发育过程。癌症相关的 EMT 并不仅仅是获得迁移和侵袭能力的简单过程,而是一个复杂而全面的重编程过程,涉及代谢、表观遗传学和分化,通过这个过程,分化的上皮癌细胞逆转到未分化状态,不仅表达干细胞标志物,而且获得类似干细胞的功能。在这里,我们回顾了最近的一些观点和发现,这些观点和发现阐明了 EMT 过程中代谢、表观遗传学和去分化之间的联系,特别强调了癌症相关 EMT 的主要驱动力和最终目标——为了能量和利用能量。此外,我们还强调了 EMT 过程中表观遗传修饰的特异性,旨在解释如何通过 EMT 同时协调上皮基因的抑制和间充质基因的激活。最后,我们对基于表观遗传和代谢水平的抗 EMT 治疗方法进行了展望,并讨论了其在临床应用中的潜力。