Tian Huajian, Wang Wenjun, Meng Xiao, Wang Miaomiao, Tan Junyang, Jia Wenjuan, Li Peining, Li Jianshuang, Zhou Qinghua
The First Affiliated Hospital, Biomedical Translational Research Institute, Jinan University, Guangzhou, China.
Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, China.
Front Cell Dev Biol. 2020 Jan 21;7:375. doi: 10.3389/fcell.2019.00375. eCollection 2019.
Gastric cancer (GC), a common type of malignant cancer, remains the fifth most frequently diagnosed cancer and the third leading cause of cancer-related deaths worldwide. Despite developments in the treatment of GC, the prognosis remains poor. Embryonic stem cell-expressed Ras (ERas), a novel member of the Ras protein family, has recently been identified as an oncogene involved in the tumorigenic growth of embryonic stem cells. A recent study reported that ERas is expressed in most GC cell lines and GC specimens, and it promotes tumorigenicity in GC through induction of the epithelial mesenchymal transition (EMT) and activation of the PI3K/AKT pathway. Here, we found that ERas blocked autophagy flux in BGC-823 and AGS GC cells, which may occur through activation of the AKT/mTOR signaling pathway. Moreover, ERas overexpression suppressed cisplatin-induced apoptosis, and rapamycin treatment significantly attenuated ERas-mediated cisplatin resistance in GC cells. These data suggest that ERas may be a potential therapeutic target to improve the outcomes of GC patients by regulating the autophagy process.
胃癌（GC）是一种常见的恶性肿瘤，仍然是全球第五大最常被诊断出的癌症，也是癌症相关死亡的第三大主要原因。尽管胃癌治疗取得了进展，但其预后仍然很差。胚胎干细胞表达的Ras（ERas）是Ras蛋白家族的一个新成员，最近被确定为参与胚胎干细胞致瘤生长的致癌基因。最近的一项研究报告称，ERas在大多数GC细胞系和GC标本中表达，并且它通过诱导上皮-间质转化（EMT）和激活PI3K/AKT途径促进GC的致瘤性。在这里，我们发现ERas阻断了BGC-823和AGS GC细胞中的自噬流，这可能是通过激活AKT/mTOR信号通路发生的。此外，ERas过表达抑制了顺铂诱导的细胞凋亡，雷帕霉素处理显著减弱了ERas介导的GC细胞对顺铂的耐药性。这些数据表明，ERas可能是通过调节自噬过程来改善GC患者预后的潜在治疗靶点。
