Open Access

Deubiquitinase USP9X regulates the invasion of prostate cancer cells by regulating the ERK pathway and mitochondrial dynamics

  • Authors:
    • Jinsong Zhang
    • Jiansong Wang
    • Ting Luan
    • Yigang Zuo
    • Jian Chen
    • Heng Zhang
    • Zhenni Ye
    • Haifeng Wang
    • Bing Hai
  • View Affiliations

  • Published online on: April 18, 2019     https://doi.org/10.3892/or.2019.7131
  • Pages: 3292-3304
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The ubiquitin‑specific protease 9X (USP9X) is a conserved deubiquitinase that has been investigated in several types of human cancer. However, the clinical significance and the biological roles of USP9X in prostate cancer remain unexplored. In the present study, an investigation into the expression and clinical significance of USP9X in prostate cancer revealed that USP9X expression was downregulated in prostate cancer tissues compared with that in healthy tissues. In addition, decreased USP9X expression was associated with a higher Gleason score and local invasion. Depletion of USP9X in prostate cancer LNCaP and PC‑3 cells by small interfering RNA promoted cell invasion and migration. Furthermore, USP9X depletion upregulated matrix metalloproteinase 9 (MMP9) and the phosphorylation of dynamin‑related protein 1 (DRP1). Notably, a significant increase in phosphorylated extracellular signal‑regulated kinase (ERK), an upstream activator of MMP9 and DRP1, was observed. To investigate whether ERK activation was able to increase MMP9 protein levels and induce DRP1 phosphorylation, an ERK inhibitor was used, demonstrating that ERK‑mediated MMP9 production and change in mitochondrial function was critical for the biological function of USP9X in prostate cancer cells. In conclusion, the present study demonstrated that USP9X is downregulated in prostate cancer and functions as an inhibitor of tumor cell invasion, possibly through the regulation of the ERK signaling pathway.
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June-2019
Volume 41 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zhang J, Wang J, Luan T, Zuo Y, Chen J, Zhang H, Ye Z, Wang H and Hai B: Deubiquitinase USP9X regulates the invasion of prostate cancer cells by regulating the ERK pathway and mitochondrial dynamics. Oncol Rep 41: 3292-3304, 2019
APA
Zhang, J., Wang, J., Luan, T., Zuo, Y., Chen, J., Zhang, H. ... Hai, B. (2019). Deubiquitinase USP9X regulates the invasion of prostate cancer cells by regulating the ERK pathway and mitochondrial dynamics. Oncology Reports, 41, 3292-3304. https://doi.org/10.3892/or.2019.7131
MLA
Zhang, J., Wang, J., Luan, T., Zuo, Y., Chen, J., Zhang, H., Ye, Z., Wang, H., Hai, B."Deubiquitinase USP9X regulates the invasion of prostate cancer cells by regulating the ERK pathway and mitochondrial dynamics". Oncology Reports 41.6 (2019): 3292-3304.
Chicago
Zhang, J., Wang, J., Luan, T., Zuo, Y., Chen, J., Zhang, H., Ye, Z., Wang, H., Hai, B."Deubiquitinase USP9X regulates the invasion of prostate cancer cells by regulating the ERK pathway and mitochondrial dynamics". Oncology Reports 41, no. 6 (2019): 3292-3304. https://doi.org/10.3892/or.2019.7131