三阴性乳腺癌中KIAA1522表达和作用研究  

KIAA1522 promotes triple negative breast cancer metastasis by activating the Wnt signaling pathway

作　　者：王磊[1] 张洁[1] 刘春玲 李玉凤[2] WANG Lei;ZHANG Jie;LIU Chunling;LI Yufeng(Pathology Department,Tangshan People's Hospital,Tangshan,Hebei 063001,China;Hebei Key Laboratory of Molecular Oncology,The Cancer Institute,Tangshan People's Hospital,Tangshan,Hebei 063001,China)

机构地区：[1]唐山市人民医院病理科,河北唐山063001 [2]河北省分子肿瘤学重点实验室、唐山市人民医院癌症研究所,河北唐山063001

出　　处：《安徽医药》2025年第1期44-48,共5页Anhui Medical and Pharmaceutical Journal

基　　金：河北省医学科学研究重点课题项目(20171270)。

摘　　要：目的分析三阴乳腺癌(TNBC)中KIAA1522激活对Wnt信号通路及促进肿瘤细胞转移的机制影响。方法该研究于2021年1月至2022年10月进行,收集唐山市人民医院手术治疗的三阴乳腺癌36例,TNBC癌组织依据有淋巴结转移(转移组)和无淋巴结转移(未转移组)分为两组,采用蛋白质印迹法和实时荧光定量逆转录PCR(RT-qPCR)法分别检测各组KIAA1522、含IQ模序的GTP酶活化蛋白1(IQGAP1)、β连环素(β-catenin)的蛋白及mRNA相对表达水平,免疫共沉淀法检测KIAA1522、IQGAP1分别与β-catenin的相互作用情况。结果转移组中KIAA1522、IQGAP1、β-catenin蛋白相对表达量(0.37±0.05、0.28±0.02、1.50±0.08)均高于未转移组(0.27±0.05、0.25±0.05、1.05±0.02)(P<0.05)。转移组中KIAA1522、IQGAP-1 mRNA相对表达量(0.95±0.03、1.08±0.10)高于未转移组(0.73±0.05、0.99±0.12)(P<0.05),两者呈正相关关系(r=0.55,P<0.05),β-catenin mRNA在二组中的相对表达量差异无统计学意义。免疫共沉淀显示在TNBC癌组织中KIAA1522蛋白与β-catenin蛋白无相互作用,而IQGAP1蛋白与β-catenin蛋白相互共沉淀。结论KIAA1522激活Wnt信号通路,促进TNBC肿瘤细胞的转移,机制可能与上调IQGAP1 mRNA,过表达的IQGAP1促进β-catenin蛋白累积并结合成蛋白复合物有关。Objective To analyze the mechanism of KIAA1522 activating Wnt signaling pathway and promoting tumor cell metastasis in triple negative breast cancer(TNBC).Methods The study was conducted from January 2021 to October 2022,36 cases of triple negative breast cancer treated surgically at Tangshan People´s Hospital were collected.TNBC was assigned into two groups according with lymph node metastasis(metastatic group)and without lymph node metastasis(non-metastatic group).The relative expression levels of KIAA1522,IQGAP1 andβ-catenin proteins and mRNA in each group were detected by Western blotting and RT-qPCR.The interaction of β-catenin respectively with KIAA1522 and IQGAP1 were detected by Co-Immunoprecipitation.Results The relative expression levels of KIAA1522 protein,IQGAP1 protein andβ-catenin protein in the metastatic group(0.37±0.05,0.28±0.02,1.50±0.08)were significantly higher than those in non-metastatic group(0.27±0.05,0.25±0.05,1.05±0.02)(P<0.05).The relative expressions of KIAA1522 mRNA and IQGAP1 mRNA in the metastatic group(0.95±0.03,1.08±0.10)were significantly higher than those in non-metastatic group(0.73±0.05,0.99±0.12)(P<0.05)and they were positively correlated(r=0.55,P<0.05),the relative expression ofβ-catenin mRNA in the two groups was not statistically significant.Co-immunocoprecipitation showed no interaction between KIAA1522 protein andβ-catenin protein in TNBC,in contrast,IQGAP1 protein co-precipitated withβ-catenin protein.Conclusion KIAA1522 activates Wnt signaling pathway and promotes the metastasis of TNBC,the mechanism may be related to upregulating of IQGAP1 mRNA,and then overexpression IQGAP1 promotes the accumulation ofβ-catenin proteins and the binding of protein complexes.

关 键 词：三阴性乳腺癌 KIAA1522 WNT信号通路 含IQ摸序的GTP酶活化蛋白1 Β连环素 免疫共沉淀 

分 类 号：R737.9[医药卫生—肿瘤]