PRL-3 promotes the peritoneal metastasis of gastric cancer through the PI3K/Akt signaling pathway by regulating PTEN.
PRL-3 promotes the peritoneal metastasis of gastric cancer through the PI3K/Akt signaling pathway by regulating PTEN.
复制标题
PRL-3通过调节PTEN通过PI3K/Akt信号通路促进胃癌腹膜转移
DOI：
10.3892/or.2016.5030
复制
发表时间：
2016-10
期刊：
影响因子：
4.2
通讯作者：
Chen H
中科院分区：
文献类型：
--
作者：
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
腹膜转移是进展期胃癌患者最常见的死亡原因。再生肝磷酸酶-3(PRL-3)被认为是一种癌基因，在胃癌腹膜转移中起重要作用。然而，PRL-3如何调控胃癌的侵袭和转移的机制尚不清楚。在本研究中，我们发现在伴有腹膜转移的胃癌中，PRL-3呈高表达，而磷酸酶和张力蛋白同源物(PTEN)呈弱表达。P-PTEN/PTEN比值在有腹膜转移的胃癌组织中也高于正常胃组织。在比较胃粘膜细胞系和GC细胞系时，我们也发现了同样的现象。构建了无酶活性的野生型和突变型质粒，并将其导入胃癌SGC7901细胞，结果表明只有PRL-3具有下调PTEN和引起PTEN磷酸化的酶活性。PRL-3可上调SGC7901细胞基质金属蛋白酶-2/基质金属蛋白酶-9的表达水平，促进细胞的迁移和侵袭。PRL-3基因敲除可显著降低MMP2/MMP9的表达水平，从而进一步抑制GC细胞的迁移和侵袭。PRL-3还可上调p-Akt/Akt的表达比例，提示PRL-3可能介导PI3K/Akt通路促进胃癌转移。当我们将PTEN siRNA载体导入PRL-3稳定低表达的GC细胞后，p-Akt、MMP2和MMP9的表达被逆转。总之，我们的研究结果在PRL-3和PTEN之间架起了一座桥梁；PRL-3下调了PTEN的表达，上调了PTEN的磷酸化水平并使其失活，从而激活了PI3K/Akt信号通路，上调了MMP2/MMP9的表达，从而促进了GC细胞的腹膜转移。
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.
登录
查看更多内容
影响因子：
11.5
作者：
Kato, H;Semba, S;Yokozaki, H
通讯作者：
Yokozaki, H
PRL-3通过触发NHERF1的去磷酸化和细胞质定位促进黑色素瘤的恶性进展
影响因子：
6.5
作者：
Fang, Xian-Ying;Song, Ran;Xu, Qiang
通讯作者：
Xu, Qiang
DOI：
10.1016/j.bbrc.2006.07.043
发表时间：
2006-09-15
影响因子：
3.1
作者：
Li, Zhengrong;Zhan, Wenhua;Ma, Jinping
通讯作者：
Ma, Jinping
影响因子：
2.7
作者：
Bessette, Darrell C.;Wong, Patrick C. W.;Pallen, Catherine J.
通讯作者：
Pallen, Catherine J.
影响因子：
4.7
作者：
Bermúdez Brito M;Goulielmaki E;Papakonstanti EA
通讯作者：
Papakonstanti EA