Shi Xiaofei, Wang Ruiqi
Department of Mathematics, Shanghai University, No.99, Shangda Road, Shanghai, 200444, China.
BMC Syst Biol. 2017 Sep 21;11(Suppl 4):84. doi: 10.1186/s12918-017-0457-6.
The Notch family of proteins plays a vital role in determining cell fates, such as proliferation, differentiation, and apoptosis. It has been shown that Notch1 and its ligands, Dll1 and Jag1, are overexpressed in many glioma cell lines and primary human gliomas. The roles of Notch1 in some cancers have been firmly established, and recent data implicate that it plays important roles in glioma cell fate decisions. This paper focuses on devising a specific theoretical framework that incorporates Dll1, Jag1, and Fringe in Notch1 signaling pathway to explore their functional roles of these proteins in glioma cells in the tumorigenesis and progression of human gliomas, and to study how glioma cell fate decisions are modulated by both trans-activation and cis-inhibition.
This paper presents a computational model for Notch1 signaling pathway in glioma cells. Based on the bifurcation analysis of the model, we show that how the glioma cell fate decisions are modulated by both trans-activation and cis-inhibition mediated by the Fringe protein, providing insight into the design and control principles of the Notch signaling system and the gliomas.
This paper presents a computational model for Notch1 signaling pathway in glioma cells based on intertwined dynamics with cis-inhibition and trans-activation involving the proteins Notch1, Dll1, Jag1, and Fringe. The results show that how the glioma cell fate transitions are performed by the Notch1 signaling. Transition from grade III ∼ IV with significantly high Notch1 to grade I ∼ II with high Notch1, and then to normal cells by repressing the Fringe levels or decreasing the strength of enhancement induced by Fringe.
Notch蛋白家族在决定细胞命运（如增殖、分化和凋亡）方面起着至关重要的作用。研究表明，Notch1及其配体Dll1和Jag1在许多胶质瘤细胞系和原发性人类胶质瘤中过表达。Notch1在某些癌症中的作用已得到明确证实，最近的数据表明它在胶质瘤细胞命运决定中发挥重要作用。本文重点设计一个特定的理论框架，将Dll1、Jag1和Fringe纳入Notch1信号通路，以探讨这些蛋白在人类胶质瘤发生和发展过程中在胶质瘤细胞中的功能作用，并研究胶质瘤细胞命运决定如何通过反式激活和顺式抑制进行调节。
本文提出了一个胶质瘤细胞中Notch1信号通路的计算模型。基于该模型的分岔分析，我们展示了胶质瘤细胞命运决定如何通过Fringe蛋白介导的反式激活和顺式抑制进行调节，从而深入了解Notch信号系统和胶质瘤的设计与控制原理。
本文基于涉及Notch1、Dll1、Jag1和Fringe蛋白的顺式抑制和反式激活的交织动力学，提出了一个胶质瘤细胞中Notch1信号通路的计算模型。结果表明Notch1信号如何实现胶质瘤细胞命运转变。通过抑制Fringe水平或降低Fringe诱导的增强强度，从Notch1水平显著高的III～IV级转变为Notch1水平高的I～II级，然后转变为正常细胞。
