The transcription factor Snail enhanced the degradation of E-cadherin and desmoglein 2 in oral squamous cell carcinoma cells
The transcription factor Snail enhanced the degradation of E-cadherin and desmoglein 2 in oral squamous cell carcinoma cells
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DOI：
10.1016/j.bbrc.2012.12.060
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发表时间：
2013-01-18
影响因子：
3.1
通讯作者：
Ozawa, Masayuki
中科院分区：
文献类型：
--
作者：
Kume, Kenichi;Haraguchi, Misako;Ozawa, Masayuki
上皮-间质转化（Epithelial-mesenchymal transition，EMT）是肿瘤转移级联反应中的一个关键过程，其特征是细胞间连接和细胞极性的丧失以及迁移和侵袭特性的获得。然而，启动这个复杂的EMT过程的精确分子事件知之甚少。Snail是EMT的调节因子，通过与靶基因启动子区的近端E-box相互作用抑制E-cadherin的转录。为了研究Snail在EMT中的作用，我们使用口腔鳞状细胞癌细胞系HSC-4（Snail/ HSC-4）产生稳定的Snail转染子。Snail/HSC-4细胞具有梭形间充质形态，并且相对于对照细胞具有增强的迁移和侵袭力。与这些EMT变化一致，检测到上皮标记蛋白E-钙粘蛋白和桥粒芯糖蛋白2的下调以及间充质标记蛋白波形蛋白和N-钙粘蛋白的上调。尽管有这些观察结果，E-钙粘蛋白和桥粒芯糖蛋白2的mRNA水平并没有显著降低。虽然E-钙粘蛋白和桥粒芯糖蛋白2蛋白在亲本HSC-4细胞中是稳定的，但这些蛋白在Snail/HSC-4细胞中迅速降解。降解的E-钙粘蛋白，但不桥粒芯糖蛋白2，抑制dynasore，动力蛋白依赖性内吞作用的抑制剂。因此，在HSC-4细胞中，Snail在转录和转录后调节这些蛋白质的水平。(C)2012 Elsevier Inc. All rights reserved.
Epithelial-mesenchymal transition (EMT), a key process in the tumor metastatic cascade, is characterized by the loss of cell-cell junctions and cell polarity as well as the acquisition of migratory and invasive properties. However, the precise molecular events that initiate this complex EMT process are poorly understood. Snail is a regulator of EMT that represses E-cadherin transcription through its interaction with proximal E-boxes in the promoter region of target genes. To investigate the role of Snail in EMT, we generated stable Snail transfectants using the oral squamous cell carcinoma cell line HSC-4 (Snail/ HSC-4). Snail/HSC-4 cells had a spindle-shaped mesenchymal morphology, and enhanced migration and invasiveness relative to control cells. Consistent with these EMT changes, the downregulation of epithelial marker proteins, E-cadherin and desmoglein 2, and the upregulation of mesenchymal marker proteins, vimentin and N-cadherin were detected. Despite these observations, the mRNA levels of E-cadherin and desmoglein 2 did not decrease significantly. Although E-cadherin and desmoglein 2 proteins were stable in parental HSC-4 cells, these proteins were rapidly degraded in Snail/HSC-4 cells. The degradation of E-cadherin, but not desmoglein 2, was inhibited by dynasore, an inhibitor of dynamin-dependent endocytosis. Therefore, in HSC-4 cells Snail regulates levels of these proteins both transcriptionally and post-translationally. (C) 2012 Elsevier Inc. All rights reserved.