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- Title
Glycogen synthase kinases-3β controls differentiation of malignant glioma cells.
- Authors
Li, Yan; Lu, Huimin; Huang, Yijun; Xiao, Ru; Cai, Xiaofeng; He, Songmin; Yan, Guangmei
- Abstract
Malignant gliomas persist as a major disease of morbidity and mortality in adult. Differentiation therapy has emerged as a promising candidate modality. However, the mechanism related is unknown. Here, we show that glycogen synthase kinase-3β (GSK-3β) is highly expressed and activated during the cholera toxin-induced differentiation in sensitive C6 and U87-MG malignant glioma cells, whereas the GSK-3α activity remains stable. GSK-3β inhibitors or small interfering RNA suppress the induced-differentiation in sensitive C6 cells. Conversely, overexpression of a constitutively active form of human GSK-3β (pcDNA3-GSK-3β-S9A) mutant in resistant U251 glioma cells restores their differentiation capabilities. In addition, GSK-3β triggers cyclin D1 nuclear export and subsequent degradation, which is necessary for differentiation in C6 and U251 glioma cells. Analysis of human glioma tissues further revealed overexpression of active GSK-3β. These findings suggest that GSK-3β is a differentiation fate determinant, and shed new lights on the mechanism by which GSK-3β regulates cyclin D1 degradation and cellular differentiation in gliomas.
- Publication
International Journal of Cancer, 2010, Vol 127, Issue 6, p1271
- ISSN
0020-7136
- Publication type
Article
- DOI
10.1002/ijc.25020