【摘要】 上皮间质转化(epithelial-mesenchymal transition,EMT)使上皮细胞极性和细胞间紧密连接消失,并赋予肿瘤细胞侵袭和转移的能力。本研究应用携带TAGLN2特异性沉默序列或无关序列的慢病毒载体感染食管鳞癌细胞系EC9706,建立EC9706 sh TAGLN2及阴性对照EC9706 sh Control亚细胞系。以5~80 ng/m L不同浓度或40 ng/m L TGF-β刺激EC9706 sh TAGLN2和EC9706sh Control细胞,发现与EC9706 sh Control细胞比较,EC9706 sh TAGLN2细胞中TAGLN2的表达无明显增加,同时TGF-β诱导的间质标志物如N-cadherin、Vimentin等蛋白质表达无明显升高;上皮标志物如E-cadherin表达无明显降低;TAGLN2的沉默不仅阻断了TGF-β诱导EC9706 sh TAGLN2细胞体外迁移和侵袭能力的增加,并抑制TGF-β信号通路下游分子p-Smad2/3的激活。本研究结果提示,TGF-β可能通过TAGLN2促进食管鳞癌的恶性演进,TAGLN2是潜在的食管鳞癌治疗的分子靶点之一。更多还原

【Abstract】 Epithelial-mesenchymal transition( EMT) renders the disappearance of cellular tight junctions and polarity for the enhancement of the mobile and invasive potential of epithelial cancer cells. In the present study,we infected EC9706 esophageal cancer cells with a lentiviral vector for silencing TAGLN2 and a non-specific scrambling sh Control to establish stable lines. After exposure to different concentrations( 5 ~ 80 ng/m L) for 72 hours or 40 ng/m L of TGF-β for various periods,inhibited migration and invasion was observed in EC9706 sh TAGLN2 cells, without down-regulated protein expression of E-cadherin or up-regulated N-cadherin and Vimentin compared to the EC9706 sh Control line. TAGLN2 gene silencing also suppressed the activation of p-Smad2/3,which is a critical molecule downstream of TGF-β signaling pathway. Our results suggested that TGF-β participated in the invasion and metastasis of ESCC involving TAGLN2.更多还原