GSK-3β Regulates Tumor Growth and Angiogenesis in Human Glioma Cells

Overview

Journal Oncotarget

Specialty Oncology

Date 2015 Sep 22

PMID 26388612

Citations 28

Authors

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

Bing-Hua Jiang

Affiliations

Soon will be listed here.

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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