核转录因子CDX2抑制胃癌细胞迁移、侵袭与逆转上皮-间质转化有关

Nuclear Transcription Factor CDX2 Inhibits Migration and Invasion of Gastric Cancer Cells by Reversing Epithelial-mesenchymal Transition

背景:尾型同源盒转录因子2(CDX2)是一种肠上皮细胞特异性核转录因子,正常胃黏膜组织不表达CDX2,而肠化生、异型增生和胃癌组织中存在CDX2异位表达。近年研究发现CDX2在胃癌中起抑癌基因作用。上皮-间质转化(EMT)与恶性肿瘤的侵袭、转移密切相关。目的:探讨CDX2对胃癌细胞迁移、侵袭能力的影响与EMT的关系。方法:分别将CDX2过表达质粒和干扰质粒转染入低表达和高表达CDX2的人胃癌细胞株MKN-45和AGS中,以划痕试验检测各组细胞迁移能力,Transwell小室细胞侵袭实验检测细胞侵袭能力,蛋白质印迹法检测EMT标记物表达。结果:过表达CDX2能显著抑制MKN-45细胞的迁移、侵袭能力,并上调上皮标记物E-cadherin表达,下调间质标记物vimentin表达(P<0.05);而沉默CDX2表达能显著增强AGS细胞的迁移、侵袭能力,下调E-cadherin表达,上调vimentin表达(P<0.05)。结论:CDX2表达水平改变可影响胃癌细胞的迁移、侵袭能力,并参与EMT的调控,其对胃癌细胞迁移、侵袭的抑制作用可能与逆转EMT有关,具体分子机制有待深入研究。

Background: Caudal-type homeobox transcription factor 2( CDX2),a specific nuclear transcription factor for intestinal epithelial cells,is absent in normal gastric mucosa,but ectopically expressed in intestinal metaplasia,dysplasia and gastric cancer tissues. Recently,CDX2 has been shown to have a cancer suppressor gene function in gastric cancer.Epithelial-mesenchymal transition( EMT) is recognized as closely related to invasion and metastasis of malignancies.Aims: To investigate the effect of CDX2 on migration and invasion and its correlation with EMT in gastric cancer cells.Methods: CDX2 expression plasmid and plasmid containing shRNA against CDX2 were transfected into human gastric cancer cell lines with low CDX2 expression( MKN-45) and high CDX2 expression( AGS),respectively. Effect of CDX2 on cell migration and invasion was evaluated by scratch test and Transwell chamber invasion assay,and expression of EMT markers was examined by Western blotting. Results: Overexpression of CDX2 significantly inhibited the capacities of migration and invasion,up-regulated epithelial marker( E-cadherin) expression and down-regulated mesenchymal marker( vimentin) expression in MKN-45 cells( P < 0. 05); while in AGS cells,silencing of CDX2 significantly enhanced the capacities of migration and invasion,down-regulated E-cadherin expression and up-regulated vimentin expression( P <0. 05). Conclusions: CDX2 regulates migration,invasion and EMT in gastric cancer cells. Reduced capacities of migration and invasion might be correlated with the reverse of EMT,however,the precise molecular mechanism needs to be further studied.