title: PRL-3 promotes the peritoneal metastasis of gastric cancer through the PI3K/Akt signaling pathway by regulating PTEN.
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.
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330000, P.R. China.
authors: Jianbo
authors: J
authors: Xiong
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330000, P.R. China.
authors: Zhengrong
authors: Z
authors: Li
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330000, P.R. China.
authors: Yang
authors: Y
authors: Zhang
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330000, P.R. China.
authors: Daojiang
authors: D
authors: Li
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330000, P.R. China.
authors: Guoyang
authors: G
authors: Zhang
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330000, P.R. China.
authors: Xianshi
authors: X
authors: Luo
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330000, P.R. China.
authors: Zhigang
authors: Z
authors: Jie
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330000, P.R. China.
authors: Yi
authors: Y
authors: Liu
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330000, P.R. China.
authors: Yi
authors: Y
authors: Cao
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330000, P.R. China.
authors: Zhibiao
authors: Z
authors: Le
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330000, P.R. China.
authors: Shengxing
authors: S
authors: Tan
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330000, P.R. China.
authors: Wenyu
authors: W
authors: Zou
authors: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330000, P.R. China.
authors: Peitao
authors: P
authors: Gong
authors: The Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors: Lingyu
authors: L
authors: Qiu
authors: The Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors: Yuanyuan
authors: Y
authors: Li
authors: The Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors: Huan
authors: H
authors: Wang
authors: The Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors: Heping
authors: H
authors: Chen
mesh_terms: D015153:Blotting, Western; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000556:secondary*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human