文章：

肿瘤细胞信号转导网络的动态控制

The dynamic control of signal transduction networks in cancer cells

原文发布日期：2015-08-20

DOI: 10.1038/nrc3983

类型: Review Article

开放获取: 否

要点：

1. Signal transduction networks (STNs) regulate fundamental biological processes by integrating and computing external and internal signals to adjust cellular physiology to changing environmental and intrinsic cues.
2. Much of the computing function of STNs is carried out by small network modules that function as switches, noise filters, oscillators, signal integrators and distributors, combinatorial ensembles of which can translate complex molecular reactions into accurate biological responses.
3. STN components are frequently affected in cancer by genetic mutations or epigenetic silencing, causing STN rewiring that modulates the biological effects of these genetic and epigenetic changes.
4. These STN alterations in cancer dynamically integrate intrinsic genetic and epigenetic changes with external stress factors, such as drug or radiation treatments, generating new network states that can profoundly change the ability of the cancer cells to survive, grow and spread.
5. Mathematical and computational modelling are powerful tools for the analysis of STNs and STN aberrations and for understanding and predicting the effects of mutations and therapeutic interventions in cancer.

要点翻译：

1. 信号转导网络通过整合和计算外部与内部信号来调节基本生物过程，使细胞生理状态适应不断变化的环境和内在信号。
2. 信号转导网络的计算功能主要由小型网络模块实现，这些模块发挥开关、噪声过滤器、振荡器、信号整合器和分配器的作用，其组合集合能将复杂分子反应转化为精确的生物学响应。
3. 在癌症中，信号转导网络组分常因基因突变或表观遗传沉默而受影响，导致网络重构，从而调节这些遗传和表观遗传变化的生物学效应。
4. 癌症中的这些信号转导网络改变动态整合了内在遗传和表观遗传变化与外部应激因素（如药物或放射治疗），产生新的网络状态，可能深刻改变癌细胞存活、生长和扩散的能力。
5. 数学与计算建模是分析信号转导网络及其异常的强大工具，有助于理解和预测癌症中突变及治疗干预的效果。

英文摘要：

Cancer is often considered a genetic disease. However, much of the enormous plasticity of cancer cells to evolve different phenotypes, to adapt to challenging microenvironments and to withstand therapeutic assaults is encoded by the structure and spatiotemporal dynamics of signal transduction networks. In this Review, we discuss recent concepts concerning how the rich signalling dynamics afforded by these networks are regulated and how they impinge on cancer cell proliferation, survival, invasiveness and drug resistance. Understanding this dynamic circuitry by mathematical modelling could pave the way to new therapeutic approaches and personalized treatments.

摘要翻译： 

癌症常被视为一种遗传病。然而，癌细胞之所以能展现出巨大的可塑性、演化出不同表型、适应恶劣微环境并抵御治疗攻击，很大程度上取决于信号转导网络的结构及其时空动态。本综述探讨了关于这些网络所赋予的丰富信号动态如何被调控，以及其如何影响癌细胞的增殖、存活、侵袭性和耐药性的最新概念。借助数学建模理解这一动态回路，有望为新的治疗手段和个体化治疗铺平道路。

原文链接：

The dynamic control of signal transduction networks in cancer cells