Sever Richard, Brugge Joan S
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724.
Harvard Medical School, Department of Cell Biology, Boston, Massachusetts 02115.
Cold Spring Harb Perspect Med. 2015 Apr 1;5(4):a006098. doi: 10.1101/cshperspect.a006098.
Cancer is driven by genetic and epigenetic alterations that allow cells to overproliferate and escape mechanisms that normally control their survival and migration. Many of these alterations map to signaling pathways that control cell growth and division, cell death, cell fate, and cell motility, and can be placed in the context of distortions of wider signaling networks that fuel cancer progression, such as changes in the tumor microenvironment, angiogenesis, and inflammation. Mutations that convert cellular proto-oncogenes to oncogenes can cause hyperactivation of these signaling pathways, whereas inactivation of tumor suppressors eliminates critical negative regulators of signaling. An examination of the PI3K-Akt and Ras-ERK pathways illustrates how such alterations dysregulate signaling in cancer and produce many of the characteristic features of tumor cells.
癌症是由基因和表观遗传改变驱动的,这些改变使细胞过度增殖,并逃避正常控制其存活和迁移的机制。其中许多改变映射到控制细胞生长和分裂、细胞死亡、细胞命运和细胞运动的信号通路,并且可以置于促进癌症进展的更广泛信号网络畸变的背景下,例如肿瘤微环境、血管生成和炎症的变化。将细胞原癌基因转化为癌基因的突变可导致这些信号通路的过度激活,而肿瘤抑制因子的失活则消除了信号传导的关键负调节因子。对PI3K-Akt和Ras-ERK信号通路的研究说明了这些改变如何在癌症中失调信号传导并产生肿瘤细胞的许多特征。