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POFUT1 acts as a tumor promoter in glioblastoma by enhancing the activation of Notch signaling

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Abstract

Dysregulation of protein O-fucosyl transferase 1 (POFUT1) contributes to the occurrence and progression of multiple cancers. However, whether POFUT1 has a relationship with the pathogenesis of glioblastoma (GBM) is unknown. This work was aimed at evaluating the detailed relevance of POFUT1 in GBM. Here, we demonstrated high levels of POFUT1 in GBM tissue and elucidated that GBM patients with high levels of POFUT1 had a shorter survival rate than those with low levels of POFUT1. POFUT1 knockdown in GBM cells markedly downregulated the ability to proliferate and invade, while overexpression of POFUT1 potentiated the proliferative and invasive ability of GBM cells. Further mechanistic studies indicated that silencing POFUT1 prohibited the activation of Notch signaling, leading to a reduction in the expression of HES1 and HEY1. On the contrary, overexpression of POFUT1 enhanced the activation of Notch signaling. Notably, inhibition of Notch signaling markedly reversed POFUT1-overexpression-induced tumor promotion effects in GBM cells. In addition, POFUT1 silencing markedly repressed the potential of GBM cells to form tumors in vivo. In conclusion, the data of this work indicates that POFUT1 serves a tumor promotion role in GBM by enhancing the activation of Notch signaling. This study underlines the potential role of the POFUT1/Notch axis in GBM progression and proposes POFUT1 as a promising anticancer target for GBM.

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The data and material used to support the findings of this study are available from the corresponding author upon request.

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Funding

This study was supported by the Key Research & Development Project of Shaanxi Province (2018YBXM-SF-12-2).

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Authors and Affiliations

  1. Department of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, China

    Qi Li, Jia Wang, Xudong Ma & Maode Wang

  2. Department of Ultrasonography, Xi’an People’s Hospital (Xi’an Fourth Hospital), No. 21 Jiefang Road, Xi’an, 710004, Shaanxi, China

    Lei Zhou

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  1. Qi Li
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  2. Jia Wang
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  3. Xudong Ma
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  4. Maode Wang
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Contributions

Qi Li designed the study, performed the experiments and drafted the manuscript. Jia Wang performed the experiments. Xudong Ma collected and analyzed the data. Maode Wang collected and analyzed the data. Lei Zhou designed the study and revised the manuscript. All authors have read and approved the final version of this manuscript.

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Correspondence to Lei Zhou.

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The clinical and animal experiments in this work were approved by the Ethics Committee of Xi’an Jiaotong University Health Science Center.

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Li, Q., Wang, J., Ma, X. et al. POFUT1 acts as a tumor promoter in glioblastoma by enhancing the activation of Notch signaling. J Bioenerg Biomembr 53, 621–632 (2021). https://doi.org/10.1007/s10863-021-09912-5

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  • DOI: https://doi.org/10.1007/s10863-021-09912-5

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