SATB1高表达通过促进上皮-间充质转化而介导鼻咽癌细胞侵袭和转移

Over-expression of SATB1 mediates invasion and metastasis of nasopharyngeal carcinoma cells through epithelial-mesenchymal transition

目的:探讨鼻咽癌(NPC)中特殊富含AT序列结合蛋白1(SATB1)的表达及其与肿瘤侵袭和转移的关系。方法:免疫组化检测76例临床NPC及61例对照鼻咽黏膜慢性炎症(NPI)组织样本中SATB1、上皮型钙黏蛋白(E-cadherin)和波形蛋白(vimentin)的表达,并分析NPC中SATB1与患者临床参数、E-cadherin和vimentin表达的相关性。体外培养不同分化状态的NPC细胞系CNE1、CNE2Z及C666-1,筛选出SATB1高表达细胞系,采用小干扰RNA(siRNA)沉默SATB1表达后,分析上皮-间充质转化(EMT)相关分子的表达及细胞侵袭能力的改变。结果:临床鼻咽组织中SATB1表达定位于胞质和胞核,NPC组中SATB1阳性表达率显著高于对照NPI组(P<0.01);E-cadherin在NPI黏膜上皮中呈膜阳性表达,NPC中膜表达水平下降,但出现胞质阳性。NPI中E-cadherin膜阳性率为100%,显著高于NPC的32.89%(P<0.01)。Vimentin呈胞质阳性,NPI上皮细胞中均阴性,但NPC中阳性率为51.32%(P<0.01)。NPC中SATB1高表达与患者性别、年龄及N分期无关,但与T分期和M分期均呈正相关(P<0.05);SATB1高表达与vimentin呈正相关(r=0.358,P=0.009)。NPC细胞系中SATB1表达与细胞分化水平呈负相关。采用siRNA敲减C666-1细胞中SATB1表达后,E-cadherin表达上升,vimentin表达下降,且细胞侵袭能力下降。结论:SATB1高表达通过促进EMT而介导NPC临床进展。

AIM:To analyze the high expression of special AT-rich sequence-binding protein 1(SATB1)in nasopharyngeal carcinoma(NPC)and its role in tumor invasion and metastasis.METHODS:The method of immunohistochemistry was used to detect the expression of SATB1 and epithelial-mesenchymal transition(EMT)-related molecules E-cadherin and vimentin in 76 cases of NPC and 61 cases of nasopharyngeal chronic inflammation(NPI),and the correlations of over-expression of SATB1 with NPC patients’clinical parameters as well as the expression of E-cadherin and vi-mentin were analyzed.Variously differentiated NPC cell lines CNE1,CNE2Z and C666-1 were cultured in vitro,and then SATB1-overexpressing cell line was screened.After interfering with SATB1 expression by siRNA,the expression of EMT-related molecules and the change of cell invasiveness were analyzed.RESULTS:The expression of SATB1 in the nasopharyngeal tissue was dominantly localized in the nuclei.The positive rate of SATB1 in NPC group was significantly higher than that in NPI group(P<0.01).E-cadherin was membrane-positive in NPI epithelial cells,while membrane E-cadherin in NPC was decreased but cytoplasmic expression was increased.The positive expression rate of membrane E-cadherin in NPI was significantly higher than that of NPC(P<0.01).Vimentin was localized in cytoplasm and negative in NPI epithelial cells,but the positive rate in NPC parenchymal cells was significant higher than that in NPI(P<0.01).The high expression of SATB1 in NPC was not related to the patents’sex,age,clinical classification and N classification,but positively correlated with T and M classification(P<0.05).Besides,high expression of SATB1 was positively correlated with vi-mentin in NPC tissues(r=0.358,P=0.009).SATB1 expression in NPC cell lines was negatively correlated with the levels of cell differentiation.Knockdown of SATB1 expression in C666-1 cells with siRNA was accompanied by an increase in E-cadherin and a decrease in vimentin levels,as well as a decrease in cell invasiveness.CONCLUSION:High expression of SATB1 promotes the clinical progress of NPC through EMT mechanism.