MUC1 drives epithelial-mesenchymal transition in renal carcinoma through Wnt/β-catenin pathway and interaction with SNAIL promoter
MUC1 drives epithelial-mesenchymal transition in renal carcinoma through Wnt/β-catenin pathway and interaction with SNAIL promoter
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DOI：
10.1016/j.canlet.2013.12.029
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发表时间：
2014-05-01
期刊：
影响因子：
9.7
通讯作者：
Perrais, Michael
中科院分区：
文献类型：
--
作者：
Gnemmi, Viviane;Bouillez, Audrey;Perrais, Michael
MUC1在人类肿瘤中高表达。转录因子Snail可以激活癌细胞的上皮间充质转化(EMT)。在本研究中，我们发现：(I)MUC1和Snail在人肉瘤样癌中高表达，(Ii)Snail间接增加MUC1的表达，(Iii)MUC1超表达诱导EMT，(Iv)MUC1C末端结构域(MUC1C)和p-catenin通过与其启动子相互作用而增加Snail的转录活性，(V)阻断MUC1C的核定位降低Wnt/β-catenin信号通路的激活和Snail的表达。综上所述，我们的发现表明MUC1是EMT中的一个参与者，并成为一个新的治疗靶点。(C)2013爱思唯尔爱尔兰有限公司。保留所有权利。
MUC1 is overexpressed in human carcinomas. The transcription factor SNAIL can activate epithelial mesenchymal transition (EMT) in cancer cells. In this study, in renal carcinoma, we demonstrate that (i) MUC1 and SNAIL were overexpressed in human sarcomatoid carcinomas, (ii) SNAIL increased indirectly MUC1 expression, (iii) MUC1 overexpression induced EMT, (iv) MUC1 C-terminal domain (MUC1-C) and p-catenin increased SNAIL transcriptional activity by interaction with its promoter and (v) blocking MUC1-C nuclear localization decreased Wnt/beta-catenin signaling pathway activation and SNAIL expression. Altogether, our findings demonstrate that MUC1 is an actor in EMT and appears as a new therapeutic target. (C) 2013 Elsevier Ireland Ltd. All rights reserved.