Department of Physics and Institute of Biophysics, Central China Normal University, Wuhan, 430079, China.
Department of Mathematics and Physics, Xuzhou Medical University, Xuzhou, 221004, China.
Sci Rep. 2018 Sep 25;8(1):14323. doi: 10.1038/s41598-018-32737-z.
Based on the transcriptional regulatory mechanisms between microRNA-200 and transcription factor ZEB in an individual cancer cell, a minimal dynamic model is proposed to study the epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) processes of cancer cells. It is shown that each cancer cell can exit in any of three phenotypic states: the epithelial (E) state, the mesenchymal (M) state, and the epithelial/mesenchymal (E/M) hybrid state, and the state of cancer cell can interconvert between different states. The phase diagram shows that there are monostable, bistable, and tristable phenotypic states regions in a parameters plane. It is found that different pathway in the phase diagram can correspond to the EMT or the MET process of cancer cells, and there are two possible EMT processes. It is important that the experimental phenomenon of E/M hybrid state appearing in the EMT process but rather in the MET process can be understood through different pathways in the phase diagram. Our numerical simulations show that the effects of noise are opposite to these of time delay on the expression of transcription factor ZEB, and there is competition between noise and time delay in phenotypic transitions process of cancer cells.
基于单个癌细胞中 microRNA-200 和转录因子 ZEB 之间的转录调控机制，提出了一个最小动态模型来研究癌细胞的上皮-间充质转化 (EMT) 和间充质-上皮转化 (MET) 过程。结果表明，每个癌细胞都可以退出三种表型状态中的任意一种：上皮 (E) 状态、间充质 (M) 状态和上皮/间充质 (E/M) 混合状态，癌细胞的状态可以在不同状态之间相互转换。相图表明，在参数平面上存在单稳、双稳和三稳表型状态区域。结果发现，相图中的不同途径可以对应于癌细胞的 EMT 或 MET 过程，并且存在两种可能的 EMT 过程。重要的是，通过相图中的不同途径可以理解 E/M 混合状态出现在 EMT 过程中而不是 MET 过程中的实验现象。我们的数值模拟表明，噪声对转录因子 ZEB 表达的影响与时间延迟的影响相反，并且噪声和时间延迟在癌细胞表型转变过程中存在竞争。
