Open Access

Polo‑like kinase 4 promotes tumorigenesis and induces resistance to radiotherapy in glioblastoma

  • Authors:
    • Jia Wang
    • Jie Zuo
    • Maode Wang
    • Xudong Ma
    • Ke Gao
    • Xiaobin Bai
    • Ning Wang
    • Wanfu Xie
    • Hao Liu
  • View Affiliations

  • Published online on: February 14, 2019     https://doi.org/10.3892/or.2019.7012
  • Pages: 2159-2167
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Glioblastoma (GBM) is one of the most malignant tumors in adults, associated with severe outcomes (median survival, <2 years). Multiple mechanisms are known to be involved in tumor recurrence and treatment resistance in GBM, however, the key regulator for GBM tumorigenesis and therapy resistance remains unclear. To clarify a novel potential functional mechanism of GBM recurrence, a wide range of experiments including in vitro molecular biological experiments and in vivo intracranial xenograft tumor models were performed in the present study. With bioinformatics analysis, polo‑like kinase 4 (PLK4) was initially identified as one of the most upregulated kinase encoding genes in GBM, which was functionally required for both in vitro cell proliferation and in vivo tumorigenesis in GBM. Clinically, an elevated PLK4 expression was observed in high grade glioma patients, which was associated with poor prognosis. In addition, PLK4 enhanced radioresistance in GBM, while PLK4 knockdown via lentivirus transfection significantly increased the radiosensitivity of GBM cells. Mechanically, PLK4 expression was markedly elevated by the exogenous overexpression of ATPase family AAA domain‑containing protein 2 (ATAD2) in GBM cells. Collectively, the results suggested that the ATAD2‑dependent transcriptional regulation of PLK4 promoted cell proliferation and tumorigenesis, as well as radioresistance in GBM, thus potentially inducing tumor recurrence. PLK4 could therefore serve as a potential therapeutic target for GBM treatment.

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April 2019
Volume 41 Issue 4

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Online ISSN:1791-2431

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Copy and paste a formatted citation
APA
Wang, J., Zuo, J., Wang, M., Ma, X., Gao, K., Bai, X. ... Liu, H. (2019). Polo‑like kinase 4 promotes tumorigenesis and induces resistance to radiotherapy in glioblastoma. Oncology Reports, 41, 2159-2167. https://doi.org/10.3892/or.2019.7012
MLA
Wang, J., Zuo, J., Wang, M., Ma, X., Gao, K., Bai, X., Wang, N., Xie, W., Liu, H."Polo‑like kinase 4 promotes tumorigenesis and induces resistance to radiotherapy in glioblastoma". Oncology Reports 41.4 (2019): 2159-2167.
Chicago
Wang, J., Zuo, J., Wang, M., Ma, X., Gao, K., Bai, X., Wang, N., Xie, W., Liu, H."Polo‑like kinase 4 promotes tumorigenesis and induces resistance to radiotherapy in glioblastoma". Oncology Reports 41, no. 4 (2019): 2159-2167. https://doi.org/10.3892/or.2019.7012