GSK-3β regulates tumor growth and angiogenesis in human glioma cells
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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
Bing-Hua Jiang, e-mail: firstname.lastname@example.org
Lianshu Ding, e-mail: email@example.com
Keywords: GSK-3β, glioma, tumor growth, angiogenesis, mTOR
Received: February 16, 2015 Accepted: August 28, 2015 Published: September 10, 2015
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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