SOX2和CTBP1相互作用对非小细胞肺癌转移的意义

Significance of SOX2 and CTBP1 interaction in metastasis of non-small cell lung cancer

目的探讨SOX2和CTBP1异常表达在非小细胞肺癌(NSCLC)转移中的作用机制。方法 Western blot检测新鲜NSCLC组织及相应的癌旁组织中SOX2和CTBP1蛋白表达;免疫沉淀法分析SOX2和CTBP1在非小细胞肺癌细胞和组织中有无相互作用;用免疫组织化学染色法(IHC)检测114例NSCLC石蜡标本中SOX2和CTBP1蛋白表达;通过转染质粒分析SOX2-CTBP1相互作用的调节机制及其对非小细胞肺癌转移的影响。结果 SOX2和CTBP1的表达水平在肺癌组织中要明显高于癌旁组织(P<0.05);SOX2-CTBP1能形成复合物,SOX2、CTBP1在NSCLC转移组中的表达水平明显高于非转移组的表达水平(P<0.05)。CTBP1的高表达与肿瘤分期、组织分化程度﹑SOX2表达、Ki-67表达相关(P<0.05)。在细胞水平,干扰CTBP1表达可下调SOX2及其下游靶基因Snail的表达,从而使H1299细胞体外迁移能力受到抑制。结论 SOX2和CTBP1的异常表达可能与NSCLC发生、发展有关,并且SOX2-CTBP1相互作用可能促进了NSCLC的侵袭转移。

Objective To investigate the mechanism and expression of SOX2 and CTBP1 protein in the metastasis of non-small cell lung cancer（ NSCLC）. Methods Western blot was used to detect the expression of SOX2 and CTBP1 in fresh lung cancer tissues and corresponding paraneoplastic tissues. Immunoprecipitation was used to analyze the interaction between SOX2 and CTBP1 in the cells and tissues of non-small cell lung cancer. SOX2 and CTBP1 expression was assessed by immunohistochemistry in 114 paraffin-embedded sections. The regulatory mechanism of SOX2-CTBP1 interaction and its effect on metastasis of non-small cell lung cancer were assessed by plasmid transduction. Results The expression of SOX2 and CTBP1 were was significantly higher in NSCLC tissues than that of paired paraneoplastic tissues（ P〈0. 05）. CTBP1 could interact with SOX2 in NSCLC tissues and cells. The expression of SOX2 and CTBP1 were higher in tumor metastasis group compared with non-metastasis group（ P〈0. 05）.The high expression of CTBP1 protein is significantly related with NSCLC clinical stage,histological differentiation,SOX2 expression and Ki-67 expression（ P〈0. 05）. At the cell level,interfering with CTBP1 expression can down regulate the expression of SOX2 and its downstream target gene Snail,so that the migration ability of H1299 cells isinhibited in vitro. Conclusions CTBP1 or SOX2 abnormal expression is potentially related to occurrence and development of NSCLC,and the interaction may promote the invasion and metastasis of NSCLC.