FAT1通过调控Hippo信号通路抑制食管鳞癌细胞增殖  

FAT1 inhibits the proliferation of esophageal squamous cell carcinoma by regulating Hippo signaling pathway

作　　者：张凡玉 陕程远 翟元芳 邹思威 李国栋[4] 胡晓玲[1,2,3] ZHANG Fanyu;SHAN Chengyuan;ZHAI Yuanfang;ZOU Siwei;LI Guodong;HU Xiaoling(Department of Pharmacology,Shanxi Medicial University,Shanxi Taiyuan 030001,China;Key Laboratory of Cellular Physiology of the Ministry of Education,Shanxi Medicial University,Shanxi Taiyuan 030001,China;Translational Medicine Research Center,Shanxi Medicial University,Shanxi Taiyuan 030001,China;Department of Otolaryngology,the Fifth Clinical Medical College of Shanxi Medical University,Shanxi Taiyuan 030012,China.)

机构地区：[1]山西医科大学药理教研室,山西太原030001 [2]山西医科大学细胞生理学教育部重点实验室,山西太原030001 [3]山西医科大学转化医学研究中心,山西太原030001 [4]山西医科大学第五临床医学院耳鼻喉科,山西太原030012

出　　处：《现代肿瘤医学》2023年第5期794-799,共6页Journal of Modern Oncology

基　　金：山西省自然科学研究面上项目(编号:202203021211226,202103021224368);国家自然科学基金项目(编号:81802825)。

摘　　要：目的:探讨FAT非典型性钙黏蛋白1(FAT atypical cadherin 1,FAT1)对食管鳞癌(esophageal squamous cell carcinoma,ESCC)细胞增殖的影响和可能的分子机制。方法:利用TCGA数据库进行FAT1的突变和生存分析;利用慢病毒构建FAT1敲低稳转株;利用MTT法和克隆形成检测FAT1对KYSE450和TE9细胞系增殖的影响;利用Western Blot检测Hippo通路相关标志物的表达;免疫组化检测Yes1相关转录调控因子(Yes1 associated transcriptional regulator,YAP)在动物组织水平中的表达。结果:TCGA数据库分析显示FAT1在31种肿瘤中存在突变。FAT1高表达的ESCC患者预后较好。FAT1敲低促进ESCC细胞的增殖,且Hippo信号通路相关基因的蛋白水平发生改变。免疫组化结果显示FAT1敲低后增强YAP在细胞核中的表达。结论:FAT1通过调控Hippo通路抑制ESCC细胞增殖。Objective:To investigate the effect and possible molecular mechanism of FAT atypical cadherin 1(FAT1)on cell proliferation of esophageal squamous cell carcinoma(ESCC).Methods:FAT1 mutation and survival analysis were performed by using TCGA databases.Lentivirus were used to construct cell lines for stable FAT1 knockdown.The effect of FAT1 on cell proliferation was detected by MTT and colony formation assay in KYSE450 and TE9 cell lines.The expressions of Hippo signaling pathway related markers were detected by Western Blot.And expression of Yes1 associated transcriptional regulator(YAP)at animal tissue level was detected by immunohistochemistry.Results:The analysis of TCGA database showed that FAT1 was mutated across 31 cancer types.ESCC patients with high FAT1 expression had a better prognosis.FAT1 knockdown promoted the proliferation of ESCC cells and changed the protein level of Hippo signaling pathway related genes.And immunohistochemistry results showed that FAT1 knockdown enhanced the expression of YAP in the nucleus.Conclusion:FAT1 inhibits ESCC cell proliferation by regulating Hippo signaling pathway.

关 键 词：食管鳞癌 FAT1 Hippo信号通路 增殖 

分 类 号：R735.1[医药卫生—肿瘤]