Mathematical modeling reveals a critical role for cyclin D1 dynamics in phenotype switching during glioma differentiation

作者：Sun, Xiaoqiang^*; Zheng, Xiaoke; Zhang, Jiajun; Zhou, Tianshou; Yan, Guangmei; Zhu, Wenbo

来源：FEBS LETTERS, 2015, 589(18): 2304-2311.

DOI：10.1016/j.febslet.2015.07.014

• Phenotype switching
• Cyclin D1
• Glioma differentiation
• Mathematical modeling

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.

• 出版日期2015-8-19
• 单位上海生物信息技术研究中心; 中山大学