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TUSC3 suppresses glioblastoma development by inhibiting Akt signaling

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Tumor Biology

Abstract

Glioblastoma multiform is one of the most common and most aggressive brain tumors in humans. The molecular and cellular mechanisms responsible for the onset and progression of GBM are elusive and controversial. The function of tumor suppressor candidate 3 (TUSC3) has not been previously characterized in GBM. TUSC3 was originally identified as part of an enzyme complex involved in N-glycosylation of proteins, but was recently implicated as a potential tumor suppressor gene in a variety of cancer types. In this study, we demonstrated that the expression levels of TUSC3 were downregulated in both GBM tissues and cells, and also found that overexpression of TUSC3 inhibits GBM cell proliferation and invasion. In addition, the effects of increased levels of methylation on the TUSC3 promoter were responsible for decreased expression of TUSC3 in GBM. Finally, we determined that TUSC3 regulates proliferation and invasion of GBM cells by inhibiting the activity of the Akt signaling pathway.

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Acknowledgments

This study was supported by the International S&T Cooperation Program of China (no. 2014DFA31630), the National Nature Science Foundation of China (nos. 81571646, 81471326, 81500924, 81572472, 81501050, and 81571108), the Specialized Research Fund for the Doctoral Program of Higher Education (no. 20132307110029), the Scientific and Technology Research Fund of the Heilongjiang Education Department (no. 12541469), the Natural Science Foundation of Heilongjiang Province (nos. H201348, H201434, and H2015062), and the Application Technology Research and Development Project of Heilongjiang Province (nos. GA15C108 and GA15C103-01).

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Authors and Affiliations

  1. Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, Heilongjiang Province, 150001, China

    Zhenfeng Jiang, Xiangtong Zhang, Li Liu, Liwei Zhao, Chuncheng Xie, Hongsheng Liang, Haiyang Wang, Minwei Zhu, Li Hu, Yuanyuan Song, Hong Shen & Zhiguo Lin

  2. Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China

    Mian Guo

  3. Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, China

    Lifen Yao

  4. Orthopaedic Hospital Research Center, University of California, Los Angeles, CA, USA

    Jia Shen

  5. Department of Operating Rooms, The First Affiliated Hospital of Harbin Medical University, Harbin, China

    Guizhen Ma

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  1. Zhenfeng Jiang
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  2. Mian Guo
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  3. Xiangtong Zhang
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Correspondence to Zhiguo Lin.

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Jiang, Z., Guo, M., Zhang, X. et al. TUSC3 suppresses glioblastoma development by inhibiting Akt signaling. Tumor Biol. 37, 12039–12047 (2016). https://doi.org/10.1007/s13277-016-5072-4

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