FYN promotes gastric cancer metastasis by activating STAT3-mediated epithelial-mesenchymal transition
FYN promotes gastric cancer metastasis by activating STAT3-mediated epithelial-mesenchymal transition
复制标题
FYN通过激活STAT3介导的上皮间质转化促进胃癌转移
DOI：
10.1016/j.tranon.2020.100841
复制
发表时间：
2020-11-01
影响因子：
5
通讯作者：
Zhang, ChangHua
中科院分区：
文献类型：
--
作者：
Yu, Jie;Zhou, ZhiJun;Zhang, ChangHua
胃癌是世界上最致命的癌症之一。FYN是一种在胃癌中差异表达的基因，被认为是几种实体瘤中关键的转移调节因子，但其在胃癌中的作用仍不清楚。本研究旨在评价FYN的作用，并检测FYN是否通过STAT 3信号通路促进胃癌细胞在体外和体内的迁移和侵袭。FYN在胃癌组织中过表达，且与转移呈正相关。FYN敲低显著降低癌细胞的迁移和侵袭，而FYN过表达增加癌细胞的迁移和侵袭。FYN的基因抑制减少了体内转移性肺结节的数量。几种上皮-间质转化标志物与FYN表达呈正相关，表明FYN参与了这种转化。此外，癌症基因组图谱数据集的基因集富集分析显示，STAT 3信号通路与FYN表达呈正相关。STAT 3抑制逆转了FYN介导的上皮-间质转化并抑制了转移。结论：FYN可能通过激活STAT 3介导的上皮间质转化促进胃癌转移，可能成为胃癌治疗的新靶点。
Gastric cancer is one of the most lethal cancers worldwide. FYN, a gene that is differentially expressed in gastric cancer, is considered a critical metastasis regulator in several solid tumors, but its role in gastric cancer is still unclear. This study aimed to evaluate the role of FYN and test whether FYN promotes migration and invasion of gastric cancer cells in vitro and in vivo via STAT3 signaling. FYN was overexpressed in gastric cancer and positively correlated with metastasis. FYN knockdown significantly decreased cancer cell migration and invasion, whereas FYN overexpression increased cancer migration and invasion. Genetic inhibition of FYN decreased the number of metastatic lung nodules in vivo. Several epithelial-mesenchymal transition markers were positively correlated with FYN expression, indicative of FYN involvement in this transition. Furthermore, gene set enrichment analysis of a Cancer Genome Atlas dataset revealed that the STAT3 signaling pathway was positively correlated with FYN expression. STAT3 inhibition reversed the FYN-mediated epithelial-mesenchymal transition and suppressed metastasis. In conclusion, FYN promotes gastric cancer metastasis possibly by activating STAT3-mediated epithelial mesenchymal transition and may be a novel therapeutic target for gastric cancer.