School of Biological Sciences, University of Auckland, Auckland 1142, New Zealand.
Front Biosci (Landmark Ed). 2011 Jan 1;16(1):307-14. doi: 10.2741/3689.
The diversity of cell populations is regulated by extracellular and intracellular variability. The latter includes genetic, epigenetic and stochastic variability, all contributing to the experimentally observed heterogeneity in response to external death-inducing stimuli. Studies of sources and regulation of variability in commitment to apoptotic cancer cell death are likely to identify the fundamental features of apoptotic protein networks that are responsible for determining the ultimate cell fate. Systems biology approaches, involving computer simulations of the biochemical reactions accompanied, if possible, by experimental verification of selected components of the model, are proving useful in determining the origins of cell-to-cell variability in response to external stress stimuli. Here we summarize our current understanding of the origins of stochastic variability in cells' commitment to apoptosis, and its implications in the field on cancer therapy.
细胞群体的多样性受到细胞外和细胞内变异性的调节。后者包括遗传、表观遗传和随机变异性，所有这些都导致了对外界诱导死亡刺激的反应的实验观察到的异质性。对凋亡性癌细胞死亡的承诺中变异性的来源和调节的研究，很可能确定负责决定最终细胞命运的凋亡蛋白网络的基本特征。系统生物学方法涉及生化反应的计算机模拟，如果可能的话，还涉及对模型的选定组成部分进行实验验证，这些方法在确定细胞对外界应激刺激的反应中的细胞间变异性的起源方面证明是有用的。在这里，我们总结了我们目前对细胞凋亡承诺中随机变异性的起源的理解，以及它在癌症治疗领域的意义。
