Department of Pathophysiology, The Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, Guangdong Province, China.
J Cell Sci. 2012 Jan 1;125(Pt 1):81-91. doi: 10.1242/jcs.086132. Epub 2012 Jan 20.
Metastasis involves tumor cell detachment from the primary tumor, and acquisition of migratory and invasive capabilities. These capabilities are mediated by multiple events, including loss of cell-cell contact, an increase in focal adhesion turnover and failure to maintain a normal cell polarity. We have previously reported that silencing of the expression of the zipcode-binding protein IMP1/ZBP1 in breast tumor patients is associated with metastasis. IMP1/ZBP1 selectively binds to a group of mRNAs that encode important mediators for cell adhesion and motility. Here, we show that in both T47D and MDA231 human breast carcinoma cells IMP1/ZBP1 functions to suppress cell invasion. Binding of ZBP1 to the mRNAs encoding E-cadherin, β-actin, α-actinin and the Arp2/3 complex facilitates localization of the mRNAs, which stabilizes cell-cell connections and focal adhesions. Our studies suggest a novel mechanism through which IMP1/ZBP1 simultaneously regulates the local expression of many cell-motility-related mRNAs to maintain cell adherence and polarity, decrease focal adhesion turnover and maintain a persistent and directional motility.
转移涉及肿瘤细胞从原发性肿瘤上脱离，并获得迁移和侵袭的能力。这些能力是由多个事件介导的，包括细胞-细胞接触的丧失、焦点黏附周转率的增加以及无法维持正常的细胞极性。我们之前曾报道，乳腺癌患者中 zipcode 结合蛋白 IMP1/ZBP1 的表达沉默与转移有关。IMP1/ZBP1 选择性地结合一组编码细胞黏附和运动的重要介质的 mRNA。在这里，我们表明在 T47D 和 MDA231 人乳腺癌细胞中，IMP1/ZBP1 抑制细胞侵袭。ZBP1 与编码 E-钙黏蛋白、β-肌动蛋白、α-辅肌动蛋白和 Arp2/3 复合物的 mRNA 结合，促进了 mRNAs 的定位，这稳定了细胞-细胞连接和焦点黏附。我们的研究表明了一种新的机制，通过该机制，IMP1/ZBP1 同时调节许多与细胞运动相关的 mRNA 的局部表达，以维持细胞黏附和极性，减少焦点黏附周转率，并保持持续和定向的运动。
