Lowe Scott W, Cepero Enrique, Evan Gerard
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
Nature. 2004 Nov 18;432(7015):307-15. doi: 10.1038/nature03098.
Mutations that drive uncontrolled cell-cycle progression are requisite events in tumorigenesis. But evolution has installed in the proliferative programmes of mammalian cells a variety of innate tumour-suppressive mechanisms that trigger apoptosis or senescence, should proliferation become aberrant. These contingent processes rely on a series of sensors and transducers that act in a coordinated network to target the machinery responsible for apoptosis and cell-cycle arrest at different points. Although oncogenic mutations that disable such networks can have profound and varied effects on tumour evolution, they may leave intact latent tumour-suppressive potential that can be harnessed therapeutically.
驱动细胞周期失控进展的突变是肿瘤发生过程中的必要事件。但是进化在哺乳动物细胞的增殖程序中设置了多种先天性肿瘤抑制机制，一旦增殖出现异常，这些机制就会触发细胞凋亡或衰老。这些偶然过程依赖于一系列传感器和信号转导分子，它们在一个协调的网络中发挥作用，在不同点靶向负责细胞凋亡和细胞周期停滞的机制。尽管使此类网络失活的致癌突变可能对肿瘤进化产生深远而多样的影响，但它们可能会保留潜在的肿瘤抑制潜力，而这种潜力可用于治疗。
