Network biology approach to epithelial-mesenchymal transition in cancer metastasis: three stage theory.
Network biology approach to epithelial-mesenchymal transition in cancer metastasis: three stage theory.
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DOI：
10.1093/jmcb/mjv035
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发表时间：
2015-06
影响因子：
5.5
通讯作者：
Hiroshi Tanaka;S. Ogishima
中科院分区：
文献类型：
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作者：
Hiroshi Tanaka;S. Ogishima
上皮-间质转化（EMT）在促进肿瘤转移中起关键作用。本研究将肿瘤EMT视为基因调控网络（GRN）的整体结构变化，并从网络生物学的角度阐明其本质特征。我们首先将GRN的状态空间定义为GRN所有可能的激活模式的集合，然后在这个空间中引入准势场来表示每个状态的相对稳定性分布。通过从公共数据库中收集基因表达谱来凭经验确定准电位。利用数据库中诱导EMT的细胞系基因表达谱的时程数据，在状态空间中跟踪EMT过程中GRN状态的变化。结果发现，癌症EMT发生在三个连续的稳定阶段，每个阶段形成一个潜在的盆地沿着EMT的轨迹。作为确认，GRN的结构变化估计通过应用ARACNe算法相同的时间过程数据，然后应用主调节器分析提取的主要规定。发现每组主调节因子在随后的三个阶段交替活跃，导致癌症EMT期间GRN的整体结构变化。
Epithelial-mesenchymal transition (EMT) plays a critical role in promoting cancer metastasis. In this study, cancer EMT is considered as an overall structural change in the gene regulatory network (GRN), and its essential features are elucidated by the network biology approach. We first defined the state space of GRN as a set of all possible activation patterns of GRN, and then introduced the quasi-potential field into this space to show the relative stability distribution of each state. The quasi-potential was determined empirically by collecting gene expression profiles from public databases. Changes of GRN states during the EMT process were traced in the state space, by using time-course data of gene expression profiles of a cell line inducing EMT from the database. It was found that cancer EMT occurred in three sequential stable stages, each of which formed a potential basin along the EMT trajectory. As confirmation, structural changes of GRN were estimated by applying the ARACNe algorithm to the same time-course data, and then applying master regulator analysis to extract the main regulations. Each group of master regulators was found to be alternatively active in the subsequent three stages to cause overall structural changes of GRN during cancer EMT.