四跨膜蛋白CO-029介导肿瘤坏死因子诱导胆管癌上皮间质转化

CO-029 mediates TNFα/TNFαR1 induced epithelial mesenchymal transition in intrahepatic cholangiocarcinoma

目的 探讨四跨膜蛋白CO-029表达在肿瘤坏死因子α（TNFα）诱导肝内胆管癌细胞发生上皮间质转化（EMT）中的作用.方法 实时PCR与蛋白印迹法检测CO-029在胆管癌细胞和组织中的表达;利用慢病毒干扰CO-029的表达,探讨其对TNFd诱导EMT过程的影响;通过免疫共沉淀后蛋白印迹法及质谱分析证实TNFαR1在肝内胆管癌可直接或间接与四跨膜蛋白CO-029形成复合物.结果 CO-029在肝内胆管癌细胞和组织中有不同程度的表达.慢病毒干扰胆管癌细胞后CO-029表达水平显著下调;CO-029表达下调后,TNFα不能诱导胆管癌细胞发生EMT.免疫共沉淀显示TNFαR1可直接或间接与四跨膜蛋白CO-029形成复合物.结论 CO-029参与调节TNFα/TNFαR1诱导肝内胆管癌细胞发生EMT,在胆管癌的侵袭转移中发挥重要作用.

Objective To investigate the role of transmembrane protein C0-029 in epithelial mesenchymal transition （EMT） induced by tumor necrosis factor alpha （TNFα） of intrahepatic cholangiocarcinoma （ICC） cells.Methods RT-PCR and Western blot were conducted to detect the CO-029 expression in ICC cells and tissues.The effect of CO-029 silencing by lenti-virus on EMT induced by TNFα was investigated.Western blot and mass spectrometry after immunoprecipitation were used to confirm whether TNFαR1 can directly or indirectly bind with CO-029 to form complexes in ICC.Results Differential expression of CO-029 was observed in ICC cells and tissues.The expression of CO-029 was significantly reduced by lenti-viral interference in ICC cells,resulting in the failure of TNFα to induce EMT.TNFαR1 in ICC could directly or indirectly form complexes with CO-029.Conclusion CO-029 mediates TNFα/TNFαR1 induced EMT in ICC,which might play an important role in the invasion and metastasis.