Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
Trends Cell Biol. 2013 Dec;23(12):620-33. doi: 10.1016/j.tcb.2013.07.006. Epub 2013 Aug 16.
Carcinogenesis is a mechanistically complex and variable process with a plethora of underlying genetic causes. Cancer development comprises a multitude of steps that occur progressively starting with initial driver mutations leading to tumorigenesis and, ultimately, metastasis. During these transitions, cancer cells accumulate a series of genetic alterations that confer on the cells an unwarranted survival and proliferative advantage. During the course of development, however, cancer cells also encounter a physiologically ubiquitous cellular program that aims to eliminate damaged or abnormal cells: apoptosis. Thus, it is essential that cancer cells acquire instruments to circumvent programmed cell death. Here we discuss emerging evidence indicating how cancer cells adopt various strategies to override apoptosis, including amplifying the antiapoptotic machinery, downregulating the proapoptotic program, or both.
致癌作用是一个机制上复杂且多变的过程，具有大量潜在的遗传原因。癌症的发生包含一系列逐步发生的步骤，从最初的驱动突变导致肿瘤发生，最终导致转移。在这些转变过程中，癌细胞会积累一系列遗传改变，赋予细胞不必要的存活和增殖优势。然而，在发育过程中，癌细胞也会遇到一种生理上普遍存在的细胞程序，旨在消除受损或异常细胞：细胞凋亡。因此，癌细胞必须获得规避程序性细胞死亡的手段。在这里，我们讨论了一些新出现的证据，表明癌细胞如何采用各种策略来克服细胞凋亡，包括放大抗凋亡机制、下调促凋亡程序，或者两者兼而有之。
