Interaction Between Ezrin and Cortactin in Promoting Epithelial to Mesenchymal Transition in Breast Cancer Cells.
Interaction Between Ezrin and Cortactin in Promoting Epithelial to Mesenchymal Transition in Breast Cancer Cells.
复制标题
Ezrin 和 Cortactin 之间的相互作用促进乳腺癌细胞上皮向间质转化
DOI：
10.12659/msm.904124
复制
发表时间：
2017-04-01
期刊：
影响因子：
--
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
He J;Ma G;Qian J;Zhu Y;Liang M;Yao N;Ding Q;Chen L;Liu X;Xia T;Wang S
背景上皮间质转化（EMT）有助于各种类型肿瘤的转移，也是乳腺癌转移级联反应中的关键步骤。在我们之前的研究中，建立了含有人源正常乳腺组织的小鼠模型，并允许在人性化乳腺微环境中模拟人乳腺癌细胞的EMT/MET过程。材料/方法使用二维电泳（2-DE）和质谱法检测亲代MDA-MB-231及其从移植的正常人乳腺组织中生长的肿瘤（MDA-MB-231br）获得的变异亚系之间的不同蛋白质。我们敲低了 2 个细胞系（MDA-MB-231 和 SUM1315）中的埃兹蛋白。评估迁移和侵袭能力。通过实时逆转录 PCR 分析和蛋白质印迹分析检查 EMT 标记。通过组织微阵列和免疫共沉淀测试了ezrin与cortactin的关系。结果蛋白质组学分析显示亲本 MDA-MB-231 和 MDA-MB-231br 之间有 81 个差异表达蛋白。其中，ezrin和cortactin的表达以及ezrin的磷酸化显着相关，并伴有一组经典的EMT标志物。埃兹蛋白的敲除可逆转 EMT 标记物的表达，并下调 cortactin 和 EMT 转录因子。 Ezrin沉默抑制肿瘤细胞迁移和侵袭。乳腺癌组织微阵列和免疫组织化学显示埃兹蛋白和 Cortactin 之间存在显着的正相关。结论 这些研究结果表明，ezrin 与 cortactin 在促进乳腺癌 EMT 方面相关。 ezrin 和 cortactin 之间的相互作用是促进癌症转移中 EMT 过程的一种新机制。
Background Epithelial to mesenchymal transition (EMT) contributes to metastases in various types of tumors, and is also the key step in the breast cancer metastatic cascade. In our previous study, a mouse model containing human-derived normal breast tissue was established and allowed EMT/MET process of human breast cancer cells to be mimicked in a humanized mammary microenvironment. Material/Methods Two-dimensional electrophoresis (2-DE) and mass spectrometry were used to detect different proteins between parental MDA-MB-231 and its variant sub-line obtained from tumors grown in transplanted normal human breast tissue (MDA-MB-231br). We knocked down the ezrin in 2 cell lines (MDA-MB-231 and SUM1315). The migration and invasion ability was assessed. EMT markers were examined by real-time reverse transcription PCR analysis and Western blot analysis. The relationship of ezrin with cortactin was tested by tissue microarray and co-immunoprecipitation. Results Proteomic analysis revealed 81 differentially expressed proteins between parental MDA-MB-231 and MDA-MB-231br. Among these proteins, the expression of ezrin and cortactin and the phosphorylation of ezrin were significantly correlated, accompanied with a group of classic EMT makers. Knockdown of ezrin reversed the expression of EMT markers and downregulated cortactin and EMT transcription factors. Ezrin silencing inhibited tumor cell migration and invasion. Breast cancer tissue microarray and immunohistochemistry showed a significant positive association between ezrin and cortactin. Conclusions These findings indicate that ezrin is correlated with cortactin in facilitating EMT in breast cancer. The interaction between ezrin and cortactin is a novel mechanism contributing to the EMT process in cancer metastases.