Department of Oncology, Zhongda Hospital, Southeast University, Nanjing 210009, China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Acta Biochim Biophys Sin (Shanghai). 2020 Mar 18;52(3):310-319. doi: 10.1093/abbs/gmz168.
Gastric cancer is an important health problem, being the fifth most common cancer and the third leading cause of cancer-related death worldwide. Aberrant protein translation contributes to the oncogenesis and development of cancers, and upregulation of translation initiation factor eIF4A1 has been observed in several kinds of malignancies. However, the role of eIF4A1 in gastric cancer progression remains unclear. In this study, we found that the expression of eIF4A1, a component of translation initiation complex, was increased in gastric cancer. High expression of eIF4A1 was positively associated with poor tumor differentiation, late T stage, lymph node metastasis, advanced TNM stage, and poor prognosis in patients with gastric cancer. Overexpression of eIF4A1 promoted the migration and invasion of gastric cancer cells in vitro and enhanced tumor metastasis in nude mice model. Mechanism studies revealed that eIF4A1 induced epithelial-to-mesenchymal transition (EMT) of gastric cancer cells through driving the translation of SNAI1 mRNA. Together, these findings indicate that eIF4A1 promotes EMT and metastasis of gastric cancer and suggest that eIF4A1 is a potential target for the adjuvant therapy for gastric cancer patients.
胃癌是一个重要的健康问题,是全球第五大常见癌症和癌症相关死亡的第三大主要原因。异常的蛋白质翻译有助于癌症的发生和发展,并且在几种恶性肿瘤中观察到翻译起始因子 eIF4A1 的上调。然而,eIF4A1 在胃癌进展中的作用尚不清楚。在这项研究中,我们发现翻译起始复合物的组成部分 eIF4A1 在胃癌中的表达增加。eIF4A1 的高表达与肿瘤分化差、T 期晚、淋巴结转移、TNM 分期晚和胃癌患者预后不良呈正相关。eIF4A1 的过表达促进了胃癌细胞的迁移和侵袭,并增强了裸鼠模型中的肿瘤转移。机制研究表明,eIF4A1 通过驱动 SNAI1 mRNA 的翻译诱导胃癌细胞的上皮-间充质转化(EMT)。总之,这些发现表明 eIF4A1 促进了胃癌的 EMT 和转移,并提示 eIF4A1 是胃癌患者辅助治疗的潜在靶点。