Silencing GMPPB Inhibits the Proliferation and Invasion of GBM via Hippo/MMP3 Pathways.

International journal of molecular sciences 2023 Sep 28

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Glioblastoma multiforme (GBM) is a highly aggressive malignancy and represents the most common brain tumor in adults. To better understand its biology for new and effective therapies, we examined the role of GDP-mannose pyrophosphorylase B (GMPPB), a key unit of the GDP-mannose pyrophosphorylase (GDP-MP) that catalyzes the formation of GDP-mannose. Impaired GMPPB function will reduce the amount of GDP-mannose available for O-mannosylation. Abnormal O-mannosylation of alpha dystroglycan (α-DG) has been reported to be involved in cancer metastasis and arenavirus entry. Here, we found that GMPPB is highly expressed in a panel of GBM cell lines and clinical samples and that expression of GMPPB is positively correlated with the WHO grade of gliomas. Additionally, expression of GMPPB was negatively correlated with the prognosis of GBM patients. We demonstrate that silencing GMPPB inhibits the proliferation, migration, and invasion of GBM cells both in vitro and in vivo and that overexpression of GMPPB exhibits the opposite effects. Consequently, targeting GMPPB in GBM cells results in impaired GBM tumor growth and invasion. Finally, we identify that the Hippo/MMP3 axis is essential for GMPPB-promoted GBM aggressiveness. These findings indicate that GMPPB represents a potential novel target for GBM treatment.

Citation

Zi-Lu Huang, Aalaa Sanad Abdallah, Guang-Xin Shen, Milagros Suarez, Ping Feng, Yan-Jiao Yu, Ying Wang, Shuo-Han Zheng, Yu-Jun Hu, Xiang Xiao, Ya Liu, Song-Ran Liu, Zhong-Ping Chen, Xiao-Nan Li, Yun-Fei Xia. Silencing GMPPB Inhibits the Proliferation and Invasion of GBM via Hippo/MMP3 Pathways. International journal of molecular sciences. 2023 Sep 28;24(19)