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PRL-3 promotes the peritoneal metastasis of gastric cancer through the PI3K/Akt signaling pathway by regulating PTEN

  • Authors:
    • Jianbo Xiong
    • Zhengrong Li
    • Yang Zhang
    • Daojiang Li
    • Guoyang Zhang
    • Xianshi Luo
    • Zhigang Jie
    • Yi Liu
    • Yi Cao
    • Zhibiao Le
    • Shengxing Tan
    • Wenyu Zou
    • Peitao Gong
    • Lingyu Qiu
    • Yuanyuan Li
    • Huan Wang
    • Heping Chen
  • View Affiliations / Copyright

    Affiliations: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330000, P.R. China, The Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
    Copyright: © Xiong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1819-1828
    |
    Published online on: August 23, 2016
       https://doi.org/10.3892/or.2016.5030
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Abstract

Peritoneal metastasis is the most frequent cause of death in patients with advanced gastric carcinoma (GC). The phosphatase of regenerating liver-3 (PRL-3) is recognized as an oncogene and plays an important role in GC peritoneal metastasis. However, the mechanism of how PRL-3 regulates GC invasion and metastasis is unknown. In the present study, we found that PRL-3 presented with high expression in GC with peritoneal metastasis, but phosphatase and tensin homologue (PTEN) was weakly expressed. The p-PTEN/PTEN ratio was also higher in GC with peritoneal metastasis than that in the normal gastric tissues. We also found the same phenomenon when comparing the gastric mucosa cell line with the GC cell lines. After constructing a wild-type and a mutant-type plasmid without enzyme activity and transfecting them into GC SGC7901 cells, we showed that only PRL-3 had enzyme activity to downregulate PTEN and cause PTEN phosphorylation. The results also showed that PRL-3 increased the expression levels of MMP-2/MMP-9 and promoted the migration and invasion of the SGC7901 cells. Knockdown of PRL-3 decreased the expression levels of MMP-2/MMP-9 significantly, which further inhibited the migration and invasion of the GC cells. PRL-3 also increased the expression ratio of p-Akt/Akt, which indicated that PRL-3 may mediate the PI3K/Akt pathway to promote GC metastasis. When we transfected the PTEN siRNA plasmid into the PRL-3 stable low expression GC cells, the expression of p-Akt, MMP-2 and MMP-9 was reversed. In conclusion, our results provide a bridge between PRL-3 and PTEN; PRL-3 decreased the expression of PTEN as well as increased the level of PTEN phosphorylation and inactivated it, consequently activating the PI3K/Akt signaling pathway, and upregulating MMP-2/MMP-9 expression to promote GC cell peritoneal metastasis.
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Spandidos Publications style
Xiong J, Li Z, Zhang Y, Li D, Zhang G, Luo X, Jie Z, Liu Y, Cao Y, Le Z, Le Z, et al: PRL-3 promotes the peritoneal metastasis of gastric cancer through the PI3K/Akt signaling pathway by regulating PTEN. Oncol Rep 36: 1819-1828, 2016.
APA
Xiong, J., Li, Z., Zhang, Y., Li, D., Zhang, G., Luo, X. ... Chen, H. (2016). PRL-3 promotes the peritoneal metastasis of gastric cancer through the PI3K/Akt signaling pathway by regulating PTEN. Oncology Reports, 36, 1819-1828. https://doi.org/10.3892/or.2016.5030
MLA
Xiong, J., Li, Z., Zhang, Y., Li, D., Zhang, G., Luo, X., Jie, Z., Liu, Y., Cao, Y., Le, Z., Tan, S., Zou, W., Gong, P., Qiu, L., Li, Y., Wang, H., Chen, H."PRL-3 promotes the peritoneal metastasis of gastric cancer through the PI3K/Akt signaling pathway by regulating PTEN". Oncology Reports 36.4 (2016): 1819-1828.
Chicago
Xiong, J., Li, Z., Zhang, Y., Li, D., Zhang, G., Luo, X., Jie, Z., Liu, Y., Cao, Y., Le, Z., Tan, S., Zou, W., Gong, P., Qiu, L., Li, Y., Wang, H., Chen, H."PRL-3 promotes the peritoneal metastasis of gastric cancer through the PI3K/Akt signaling pathway by regulating PTEN". Oncology Reports 36, no. 4 (2016): 1819-1828. https://doi.org/10.3892/or.2016.5030
Copy and paste a formatted citation
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Spandidos Publications style
Xiong J, Li Z, Zhang Y, Li D, Zhang G, Luo X, Jie Z, Liu Y, Cao Y, Le Z, Le Z, et al: PRL-3 promotes the peritoneal metastasis of gastric cancer through the PI3K/Akt signaling pathway by regulating PTEN. Oncol Rep 36: 1819-1828, 2016.
APA
Xiong, J., Li, Z., Zhang, Y., Li, D., Zhang, G., Luo, X. ... Chen, H. (2016). PRL-3 promotes the peritoneal metastasis of gastric cancer through the PI3K/Akt signaling pathway by regulating PTEN. Oncology Reports, 36, 1819-1828. https://doi.org/10.3892/or.2016.5030
MLA
Xiong, J., Li, Z., Zhang, Y., Li, D., Zhang, G., Luo, X., Jie, Z., Liu, Y., Cao, Y., Le, Z., Tan, S., Zou, W., Gong, P., Qiu, L., Li, Y., Wang, H., Chen, H."PRL-3 promotes the peritoneal metastasis of gastric cancer through the PI3K/Akt signaling pathway by regulating PTEN". Oncology Reports 36.4 (2016): 1819-1828.
Chicago
Xiong, J., Li, Z., Zhang, Y., Li, D., Zhang, G., Luo, X., Jie, Z., Liu, Y., Cao, Y., Le, Z., Tan, S., Zou, W., Gong, P., Qiu, L., Li, Y., Wang, H., Chen, H."PRL-3 promotes the peritoneal metastasis of gastric cancer through the PI3K/Akt signaling pathway by regulating PTEN". Oncology Reports 36, no. 4 (2016): 1819-1828. https://doi.org/10.3892/or.2016.5030
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