14-3-3β regulates the proliferation of glioma cells through the GSK3β/β-catenin signaling pathway

Gong,Fanghe; Wang,Guoliang; Ye,Jing; Li,Tiandong; Bai,Hongmin; Wang,Weimin

doi:10.3892/or.2013.2740

14-3-3β regulates the proliferation of glioma cells through the GSK3β/β-catenin signaling pathway

Authors:
- Fanghe Gong
- Guoliang Wang
- Jing Ye
- Tiandong Li
- Hongmin Bai
- Weimin Wang
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Affiliations: Department of Neurosurgery, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, P.R. China, Department of Huiqiao, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China
Published online on: September 19, 2013 https://doi.org/10.3892/or.2013.2740
Pages: 2976-2982

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Abstract

We previously demonstrated that 14-3-3β is overexpressed in astrocytomas; however, the underlying mechanisms are poorly understood. Based on the reported multiple functions of 14-3-3β, we hypothesized that it interacts with glycogen synthase kinase 3 β (GSK3β), which regulates β-catenin-mediated oncogene expression and contributes to tumorigenesis and astrocytoma progression. To test these hypotheses, we used 14-3-3β overexpression vectors and small interfering RNA (siRNA) transfection in the human normal astrocyte cell line SVGp12 and the glioma cell line U87, respectively. The results showed that overexpression of 14-3-3β promoted the proliferation of SVGp12 cells, while knockdown of 14-3-3β inhibited the proliferation of U87 cells as analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and bromodeoxyuridine (BrdU) assays. In Flag-tagged 14-3-3β-overexpressing cells, GSK3β was co-immunoprecipitated with 14-3-3β using a Flag antibody. Knockdown of β-catenin by siRNA blocked cell proliferation induced by overexpression of 14-3-3β. Furthermore, overexpression of 14-3-3β suppressed the phosphorylation of β-catenin leading to its accumulation and nuclear translocation as revealed by western blot analysis. In addition, β-catenin nuclear translocation induced by overexpression of 14-3-3β activated the transcription of oncogenes including c-myc and cyclin D1. Collectively, these results revealed that 14-3-3β regulates the proliferation of astrocytes and glioma cells through the GSK3β/β-catenin signaling pathway. The delineated mechanism of 14-3-3β may be responsible for the tumorigenesis and progression of human astrocytomas. Thus, new therapeutic strategies or drugs aimed at 14-3-3β may have potential for the treatment of human astrocytomas.

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