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

08:00 EDT 18th April 2019 | BioPortfolio

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

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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This article was published in the following journal.

Name: Oncology reports
ISSN: 1791-2431
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Medical and Biotech [MESH] Definitions

A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.

A synthetic retinoid that is used orally as a chemopreventive against prostate cancer and in women at risk of developing contralateral breast cancer. It is also effective as an antineoplastic agent.

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Proteins secreted by the prostate gland. The major secretory proteins from the human prostate gland include PROSTATE-SPECIFIC ANTIGEN, prostate-specific acid phosphatase, prostate-specific membrane antigen, and prostate-specific protein-94.

Tumors or cancer of the PROSTATE.

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