Oncotarget

Research Papers:

GSK-3β regulates tumor growth and angiogenesis in human glioma cells

Peng Zhao _, Qi Li, Zhumei Shi, Charlie Li, Lin Wang, Xue Liu, Chengfei Jiang, Xu Qian, Yongping You, Ning Liu, Ling-Zhi Liu, Lianshu Ding and Bing-Hua Jiang

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Oncotarget. 2015; 6:31901-31915. https://doi.org/10.18632/oncotarget.5043

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Abstract

Peng Zhao1,*, Qi Li2,4,*, Zhumei Shi1, Charlie Li5, Lin Wang2, Xue Liu2, Chengfei Jiang2,6, Xu Qian2,6, Yongping You1, Ning Liu1, Ling-Zhi Liu7, Lianshu Ding3, Bing-Hua Jiang2,7

1Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China

2State Key Lab of Reproductive Medicine, Department of Pathology, and Collaborative Innovation Center for Cancer Personalized Medicine, Cancer Center, Nanjing Medical University, Nanjing 210029, China

3Department of Neurosurgery, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an 223300, China

4Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing, University Medical School, Nanjing 210008, China

5Department of Environmental Toxicology, University of California-Davis, Davis, CA 94564, USA

6Ninggao Personalized Medicine and Technology Innovation Center, Nanjing 21130, China

7Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA

*These authors have contributed equally to this work

Correspondence to:

Bing-Hua Jiang, e-mail: binghjiang@hotmail.com

Lianshu Ding, e-mail: dlshu@163.com

Keywords: GSK-3β, glioma, tumor growth, angiogenesis, mTOR

Received: February 16, 2015     Accepted: August 28, 2015     Published: September 10, 2015

ABSTRACT

Background: Glioma accounts for the majority of primary malignant brain tumors in adults.

Methods: Glioma specimens and normal brain tissues were analyzed for the expression levels of GSK-3β and p-GSK-3β (Ser9) by tissue microarray analysis (TMA) and Western blotting. Glioma cells over-expressing GSK-3β were used to analyze biological functions both in vitro and in vivo.

Results: The levels of p-GSK-3β (Ser9), but not total GSK-3β, are significantly up-regulated in glioma tissues compared to normal tissues, and are significantly correlated with the glioma grades. Ectopic expression of GSK-3β decreased the phosphorylation levels of mTOR and p70S6K1; and inhibited β-catenin, HIF-1α and VEGF expression. Forced expression of GSK-3β in glioma cells significantly inhibited both tumor growth and angiogenesis in vivo.

Conclusions: These results reveal that GSK-3β regulates mTOR/p70S6K1 signaling pathway and inhibits glioma progression in vivo; its inactivation via p-GSK-3β (Ser9) is associated with glioma development, which is new mechanism that may be helpful in developing GSK-3β-based treatment of glioma in the future.


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