Fas信号通路通过诱导EMT促进胃癌细胞的侵袭转移  

Fas signaling promotes metastasis through EMT in gastric cancer

作　　者：石萌[1] 南兴建 李文静[1] 王亚东[1] 郑浩轩[1] 

机构地区：[1]广东省胃肠疾病重点实验室,南方医科大学南方医院消化内科,510515 [2]江苏省南京市江宁医院护理部,211100

出　　处：《现代消化及介入诊疗》2014年第2期71-75,共5页Modern Interventional Diagnosis and Treatment in Gastroenterology

基　　金：中国国家自然科学基金(No.81201962);广东省自然科学基金(No.S2012040006985);教育部博士点基金(No.20124433120003)~~

摘　　要：目的探讨Fas信号通路促进胃癌细胞侵袭转移的可能相关机制。方法以低浓度FasL处理胃癌细胞株AGS,免疫印迹及ELISA检测上皮间质转化(epithelial-mesenehymal transition,EMT)的分子生物学标记改变;稳定沉默Snail及Twist转录因子,transwell小室侵袭实验检测FasL处理后胃癌细胞的侵袭能力;免疫印迹检测信号通路激活状态及相应的抑制效应。结果 FasL可以诱导AGS细胞株出现EMT表型,并可促进胃癌细胞的侵袭转移能力。同时该过程中出现ERK1/2信号通路的激活,而抑制ERK1/2信号通路,可以抑制FasL诱导EMT及提高肿瘤侵袭能力的作用。胃癌组织中相应分子生物学标记的表达变化符合EMT的发生。结论 Fas信号通路能够激活ERK1/2通路诱导EMT的发生,并且能通过该机制增强胃癌细胞AGS的活动能力。Objective To explore the possible mechanisms of the metastasis promotion induced by Fas signaling pathway in gastric cancer. Methods Gastric cancer cell line AGS was treated with low-dose FasL and the alteration of EMT （epithelial-mesenehymal transition） biology markers were detected by immunoblot and enzyme linked immunosorbent assay,respectively. Two transcription factors Snail and Twist were stablely knocked-down, and transwell chamber migration assay was performed to measure the motility of the pretreated gastric cancer cells. Immunoblot was used to assess the activations and the motility changes of AGS after pre-treated with inhibitor of relative pathways during the procedure. Results FasL induced the occurrence of EMT in AGS cell line, which might contribute to the motility and metastasis of gastric cancer cells. In the process of EMT, ERK1/2 signaling pathway was activated and the suppression of this pathway inhibited the Fas induced EMT and improved the migration ability of gastric cancer cells. The expression variation of relevant biology markers in gastric cancer tissues was correspond to EMT occurrence. Conclusion Fas signaling pathway can promote the metastasis of AGS cell line through EMT with the activation of ERK1/2 pathway.

关 键 词：Fas信号通路 EMT ERK1 2信号通路 

分 类 号：R735.2[医药卫生—肿瘤]