title: Mathematical modeling reveals a critical role for cyclin D1 dynamics in phenotype switching during glioma differentiation.
abstract: 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.
authors.affiliation: Research Center of Bioinformatics, Zhong-shan School of Medicine, Sun Yat-Sen University, Guangzhou 510089, China; School of Mathematical and Computational Science, Sun Yat-Sen University, Guangzhou 510000, China. Electronic address: xiaoqiangsun88@gmail.com.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Sun
authors.affiliation: First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, China.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Zheng
authors.affiliation: School of Mathematical and Computational Science, Sun Yat-Sen University, Guangzhou 510000, China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Mathematical and Computational Science, Sun Yat-Sen University, Guangzhou 510000, China.
authors.forename: Tianshou
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, Zhong-shan School of Medicine, Sun Yat-Sen University, Guangzhou 510089, China.
authors.forename: Guangmei
authors.initials: G
authors.lastname: Yan
authors.affiliation: Department of Pharmacology, Zhong-shan School of Medicine, Sun Yat-Sen University, Guangzhou 510089, China. Electronic address: zhuwenbo@mail.sysu.edu.cn.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism*; D004357:Drug Synergism; D005910:Glioma / Q000473:pathology*; D008954:Models, Biological; D010641:Phenotype; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D019938:Cyclin D1
keywords: Cyclin D1; Glioma differentiation; Mathematical modeling; Phenotype switching