Abstract
OBJECTIVES: Gastric cancer ranks the fourth most common cancer and the third leading cause of cancer mortality in the world. ROS proto-oncogene 1 (ROS1) is an oncogene and ROS1 rearrangement has been reported in many cancers. Our study aimed to investigate the potential function and the precise mechanisms of ROS1 in gastric cancer. METHODS: In our study, the analysis of ROS1 expression and clinical pathologic factors of gastric cancer in gastric cancer using TCGA database demonstrated that ROS1 expression was elevated in gastric cancer and related to T, N, M and TNM staging. High expression of ROS1 predicted poor survival in patients with gastric cancer. Then, we measured ROS1 expression in four human gastric cancer cell lines and knocked down ROS1 expression in BGC-823 and SGC-7901 cells by specific shRNA transfection via Lipofectamine 2000. The effect of ROS1 knockdown on cell proliferation, cell cycle distribution, cell apoptosis and metastasis in vitro was evaluated by MTT, colony formation, flow cytometric analysis, wound healing and Transwell invasion assays. The levels of apoptosis-related proteins, EMT markers and the PI3K/Akt signaling pathway members were measured by Western blotting. RESULTS: We demonstrated that shROS1 transfection markedly downregulated ROS1 expression in BGC-823 and SGC-7901 cells. Knockdown of ROS1 inhibited cell survival, clonogenic growth, migration, invasion and epithelial-mesenchymal transition (EMT), as well as induced cell cycle arrest and apoptosis in gastric cancer cells. Furthermore, ROS1 knockdown inhibited the phosphorylation of PI3K and Akt. CONCLUSION: Collectively, our data suggest that ROS1 may serve as a promising therapeutic target in gastric cancer treatment.