The transcription factor Snail expressed in cutaneous squamous cell carcinoma induces epithelial-mesenchymal transition and down-regulates COX-2
The transcription factor Snail expressed in cutaneous squamous cell carcinoma induces epithelial-mesenchymal transition and down-regulates COX-2
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DOI：
10.1016/j.bbrc.2012.12.035
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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：
Shimokawa, Mitsuyoshi;Haraguchi, Misako;Ozawa, Masayuki
皮肤梭形细胞鳞状细胞癌(SCC)是一种罕见的高度恶性的SCC变种。鳞状细胞衍生的具有肉瘤样外观的纺锤形细胞的存在，表明这些细胞是上皮-间充质转化(EMT)的结果。EMT是一个复杂的过程，在这个过程中，上皮细胞失去了它们的极性和细胞与细胞的接触，同时也获得了更多的运动性和侵袭性。Snail通过与E-钙粘蛋白启动子区域近端的E-box结合并抑制其转录来调节EMT。当检测EMT标志物和Snail在梭形细胞SCCs中的表达时，我们发现环氧合酶-2(COX-2)表达下调。由于已证明COX-2在包括结肠癌、胃癌和肺癌在内的多种恶性肿瘤中呈结构性过表达，因此COX-2表达的下调是意想不到的。COX-2启动子区域存在E-box样序列促使我们进行更详细的分析。我们将Snail表达载体导入角质形成细胞来源的细胞系(Hakat、HSC5和A431细胞)，并分离到稳定的转染体。我们发现，在表达Snail的细胞中，COX-2的表达下调。与这些观察结果一致的是，记者分析表明，COX-2启动子的活性在Snail过表达时受到抑制。因此，Snail下调了这些细胞中的COX-2。(C)2012 Elsevier Inc.保留所有权利。
Cutaneous spindle cell squamous cell carcinoma (SCC) is a rare, but highly malignant variant of SCC. The presence of spindle-shaped cells with a sarcomatous appearance, which are derived from squamous cells, suggests that these cells are produced as a result of epithelial-mesenchymal transition (EMT). EMT is a complex process in which epithelial cells lose their polarity and cell-cell contacts, while also acquiring increased motility and invasiveness. Snail regulates EMT by binding to proximal E-boxes in the promoter region of E-cadherin and repressing its transcription. When examining the expression of EMT markers and Snail in spindle cell SCCs, we found that cyclooxygenase-2 (COX-2) expression was down-regulated. Since it has been shown that COX-2 is constitutively overexpressed in a variety of malignancies, including colon, gastric, and lung carcinomas, the down-regulation of COX-2 expression was unexpected. The presence of E-box-like sequences in the promoter region of COX-2 prompted us to perform a more detailed analysis. We introduced a Snail expression vector into keratinocyte-derived cell lines (HaKaT, HSC5, and A431 cells), and isolated stable transfectants. We determined that COX-2 expression was down-regulated in cells expressing Snail. Consistent with these observations, reporter assays revealed that COX-2 promoter activity was repressed upon Snail overexpression. Thus Snail down-regulates COX-2 in these cells. (C) 2012 Elsevier Inc. All rights reserved.