Journal
FEBS LETTERS
Volume 589, Issue 18, Pages 2304-2311Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2015.07.014
Keywords
Phenotype switching; Cyclin D1; Glioma differentiation; Mathematical modeling
Funding
- National Natural Science Foundation of China [81202555, 81373428]
- Guangdong Nature Science Foundation [2014A030310355]
- 985 project of Sun Yat-sen University [50000-31101302]
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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. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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