中胚层特异性转录物通过细胞外基质重塑促进胃癌细胞的侵袭

Mesoderm-specific transcripts promote invasion of gastric cancer cells through extracellular matrix remodeling

目的探索中胚层特异性转录物(MEST)通过细胞外基质重塑促进胃癌细胞的侵袭的作用及其生物学机制。方法选取2022年7―8月在晋城市人民医院确诊为胃癌的病人27例。以蛋白质印迹法检测胃癌组织和细胞中MEST的表达。在AGS和SGC-7901中分别建立了MEST沉默细胞系,研究MEST对细胞增殖、迁移、侵袭和上皮间质转化的影响。蛋白质印迹法检测Wnt/β-catenin/Twist-1信号通路相关蛋白的表达水平。在裸鼠体内种植定感染了表达sh-MEST的慢病毒的胃癌细胞系MK-45,接种后观察肿瘤生长并记录数据。结果MEST在胃癌组织和细胞系中升高。与正常胃黏膜组织相比,胃癌组织中MEST蛋白水平显著升高[(100.00±9.03)%比(824.27±70.15)%,t=83.43,P<0.001];MEST的沉默阻碍了细胞增殖、迁移和侵袭以及上皮-间质转化。蛋白质印迹法结果显示,MEST沉默后胃癌细胞E-cadherin上皮细胞标志物蛋白被上调,神经钙黏素(N-cadherin)、波形蛋白(Vimentin)、Wnt、β-catenin、Snail和Twist1等间质细胞标志蛋白的表达与之相反。转染sh-MEST抑制了胃癌细胞在活生物体内的生长。结论MEST通过Wnt/β-catenin/Twist-1信号在胃癌中发挥致癌功能,MEST可能代表了胃癌治疗的一个潜在靶标。

Objective To explore the role of mesoderm-specific transcripts(MEST)in promoting the invasion of gastric cancer cells through extracellular matrix remodeling and its biological mechanism.Methods The expression of MEST in gastric cancer tissues and cells was detected by western-blotting.MEST-shRNAs transfered in AGS and SGC-7901 respectively to study the effects of MEST on cell proliferation,migration,invasion and epithelial mesenchymal transition.Western-blotting was used to detect the expression levels of proteins related to the Wnt/β-catenin/Twist-1 signaling pathway.GC cell line MK-45 infected with MEST-shRNA was grown in nude mice,and tumor growth was observed and data recorded after inoculation.Results MEST was elevated in gastric cancer tissues and cell lines[(100.00±9.03)%vs.(824.27±70.15)%,t=83.43,P<0.001].silencing of MEST impeded cell proliferation,migration and invasion,and epithelial-mesenchymal transition.Western-blotting showed that E-cadherin epithelial cell marker protein was upregulated in gastric cancer cells after MEST silencing,in contrast to the expression of mesenchymal cell marker proteins such as N-cadherin,Vimentin,Wnt,β-catenin,Snail and Twist1.Transfection of sh-MEST inhibited the growth of gastric cancer cells in living organisms.Con⁃clusion Our data confirm that MEST exerts oncogenic functions in gastric cancer via MEST via Wnt/β-catenin/Twist-1 signaling,and that MEST may represent a potential target for gastric cancer therapy.