Liu Jun, Wei Hongquan, Lai Liqin, Wang Yuanyuan, Han Xiaoyu, Zhang Zhen
Department of Pathology, Tongde Hospital of Zhejiang Province, Hangzhou, China.
Clin Invest Med. 2019 Jun 23;42(2):E38-47. doi: 10.25011/cim.v42i2.32815.
Golgi phosphoprotein-3 (GOLPH3) is an oncogene that is overexpressed in multiple cancers and is associated with poor prognosis. The aim of this study was to examine the impact of GOLPH3 on the migration and metastasis of gastric cancer cells.
Following the shRNA-mediated knockdown of GOLPH3, we analyzed cytoskeletal reorganization and cell invasion, migration and adhesion, and determined the impact of components of the mammalian target of the rapamycin (mTOR) signalling pathway.
The GOLPH3 mRNA and protein expression were significantly lower in both SGC-7901 and MKN-28 cells as compared with poorly-differentiated BGC-823 cells. The GOLPH3 knockdown also significantly reduced cell invasion in all three cell lines through reduced migration as compared with the non-targeting control sequence group. The GOLPH3 knockdown also reduced F-actin in all three cell lines, and decreased cell adhesion in BGC-823 and SGC-7901 cells. Finally, p-mTOR, p70S6K, p-4EBP1 and RhoA protein levels were significantly downregulated in shGOLPH3-1-treated cells.
In conclusion, GOLPH3 increased in poorly-differentiated gastric cancer cells, activating the mTOR-70S6K/4EBP1-RhoA signalling pathway to promote the migration and metastasis of gastric cancer cells.
高尔基磷蛋白3（GOLPH3）是一种癌基因，在多种癌症中过度表达，且与预后不良相关。本研究旨在探讨GOLPH3对胃癌细胞迁移和转移的影响。
在通过shRNA介导敲低GOLPH3后，我们分析了细胞骨架重组以及细胞侵袭、迁移和黏附情况，并确定了雷帕霉素哺乳动物靶标（mTOR）信号通路各组分的影响。
与低分化的BGC-823细胞相比，SGC-7901和MKN-28细胞中的GOLPH3 mRNA和蛋白表达均显著降低。与非靶向对照序列组相比，敲低GOLPH3还通过减少迁移显著降低了所有三种细胞系的细胞侵袭。敲低GOLPH3还降低了所有三种细胞系中的F-肌动蛋白，并降低了BGC-823和SGC-7901细胞的细胞黏附。最后，在经shGOLPH3-1处理的细胞中，p-mTOR、p70S6K、p-4EBP1和RhoA蛋白水平显著下调。
总之，在低分化胃癌细胞中GOLPH3表达增加，激活mTOR-70S6K/4EBP1-RhoA信号通路，促进胃癌细胞的迁移和转移。
