Toward a quantitative understanding of the Wnt/-catenin pathway through simulation and experiment
Toward a quantitative understanding of the Wnt/-catenin pathway through simulation and experiment
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DOI：
10.1002/wsbm.1221
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发表时间：
2013-07-01
影响因子：
7.9
通讯作者：
Byrne, Helen M.
中科院分区：
文献类型：
--
作者：
Lloyd-Lewis, Bethan;Fletcher, Alexander G.;Byrne, Helen M.
Wnt 信号传导在整个发育过程中调节细胞存活、增殖和分化，并且在癌症中受到异常调节。当 Wnt 配体与细胞表面的特定受体结合时，该途径被激活，导致转录辅激活因子 - 连环蛋白的稳定和核积累。数学和计算模型已用于研究 Wnt/-catenin 通路的空间和时间调控，并研究关键组件突变的功能影响。此类模型的复杂性各不相同，从描述单细胞内关键通路成分之间生化相互作用的时间依赖性常微分方程，到结合 Wnt/-连环蛋白通路靶基因在组织稳态和癌发生中的作用的复杂多尺度模型。本综述旨在总结 Wnt 通路数学建模的最新进展，并强调新的生物学结果，这些结果可以为未来的理论研究奠定基础，旨在提高 Wnt 信号传导理论模型在生物医学领域的实用性。 (C) 2013 年 Wiley 期刊公司。
Wnt signaling regulates cell survival, proliferation, and differentiation throughout development and is aberrantly regulated in cancer. The pathway is activated when Wnt ligands bind to specific receptors on the cell surface, resulting in the stabilization and nuclear accumulation of the transcriptional co-activator -catenin. Mathematical and computational models have been used to study the spatial and temporal regulation of the Wnt/-catenin pathway and to investigate the functional impact of mutations in key components. Such models range in complexity, from time-dependent, ordinary differential equations that describe the biochemical interactions between key pathway components within a single cell, to complex, multiscale models that incorporate the role of the Wnt/-catenin pathway target genes in tissue homeostasis and carcinogenesis. This review aims to summarize recent progress in mathematical modeling of the Wnt pathway and to highlight new biological results that could form the basis for future theoretical investigations designed to increase the utility of theoretical models of Wnt signaling in the biomedical arena. (C) 2013 Wiley Periodicals, Inc.