Mathematical modeling reveals a critical role for cyclin D1 dynamics in phenotype switching during glioma differentiation
Mathematical modeling reveals a critical role for cyclin D1 dynamics in phenotype switching during glioma differentiation
复制标题
数学模型揭示了细胞周期蛋白 D1 动力学在神经胶质瘤分化过程中表型转换中的关键作用
DOI：
10.1016/j.febslet.2015.07.014
复制
发表时间：
2015-08
期刊：
影响因子：
3.5
通讯作者：
Zhu Wenbo
中科院分区：
文献类型：
--
作者：
Sun Xiaoqiang;Zheng Xiaoke;Zhang Jiajun;Zhou Tianshou;Yan Guangmei;Zhu Wenbo
胶质瘤分化治疗是一种利用特异性药物诱导胶质瘤细胞分化为胶质样细胞以增强抗胶质瘤效果的新模式。然而，胶质瘤分化的分子机制仍然知之甚少。在本研究中，我们建立了胶质瘤分化信号通路的实验整合数学模型。我们的建模和实验分析表明，一个“单向开关”的分叉周期蛋白D1动力学控制胶质瘤细胞的表型转变是至关重要的。我们还定量评估了药物组合的协同治疗效果。这些结果提供了深入了解胶质瘤分化的分子机制和设计新的治疗靶点在抗癌治疗中的意义。
Glioma differentiation therapy is a novel modality to increase anti-glioma effects using specific drugs to induce glioma cell differentiation to glia-like cells. However, the molecular mechanisms underlying glioma differentiation remain poorly understood. In this study, we built an experiment-integrated mathematical model for glioma differentiation signaling pathways. Our modeling and experimental analysis revealed that a “one-way-switch” bifurcation of cyclin D1 dynamics was critical for controlling the phenotypic transition of glioma cells. We also quantitatively evaluated drug combinations toward a synergistic therapeutic effect. These results provide insights into the molecular mechanisms underlying glioma differentiation and implications for the design of novel therapeutic targets in anti-cancer therapy.
登录
查看更多内容
影响因子：
6.4
作者：
Li, Yan;Lu, Huimin;Yan, Guangmei
通讯作者：
Yan, Guangmei
影响因子：
3.7
作者：
Gonze D;Abou-Jaoudé W
通讯作者：
Abou-Jaoudé W
影响因子：
5.3
作者：
M. Hitomi;D. Stacey
通讯作者：
M. Hitomi;D. Stacey
影响因子：
5.8
作者：
Swat, M;Kel, A;Herzel, H
通讯作者：
Herzel, H
影响因子：
64.5
作者：
Leder K;Pitter K;LaPlant Q;Hambardzumyan D;Ross BD;Chan TA;Holland EC;Michor F
通讯作者：
Michor F