MUC1 drives epithelial-mesenchymal transition in renal carcinoma through Wnt/β-catenin pathway and interaction with SNAIL promoter

被引:74
作者
Gnemmi, Viviane [1 ,2 ,3 ]
Bouillez, Audrey [1 ]
Gaudelot, Kelly [1 ]
Hemon, Brigitte [1 ]
Ringot, Belinda [1 ]
Pottier, Nicolas [3 ,4 ]
Glowacki, Francois [3 ,4 ,5 ]
Villers, Arnauld [3 ,6 ]
Vindrieux, David [7 ]
Cauffiez, Christelle [3 ,4 ]
Van Seuningen, Isabelle [1 ]
Bernard, David [7 ]
Leroy, Xavier [1 ,2 ,3 ]
Aubert, Sebastien [1 ,2 ,3 ]
Perrais, Michael [1 ,3 ]
机构
[1] INSERM, UMR837, Equipe Mucines Differenciat & Cancerogenese Epith, Jean Pierre Aubert Res Ctr, F-59045 Lille, France
[2] CHRU Lille, Ctr Biol Pathol, Inst Pathol, F-59037 Lille, France
[3] Univ Lille 2, Fac Med Henri Warembourg, F-59045 Lille, France
[4] Fac Med, Dept Biochem & Mol Biol, EA4483, F-59045 Lille, France
[5] CHRU Lille, Hop Huriez, Dept Nephrol, F-59037 Lille, France
[6] CHRU Lille, Hop Huriez, Dept Urol, F-59037 Lille, France
[7] Ctr Rech Cancerol Lyon, UMR CNRS INSERM 5286 1052, Lyon, France
关键词
MUC1; SNAIL; Epithelial mesenchymal transition; Beta catenin; GO-203; GROWTH-FACTOR RECEPTOR; NF-KAPPA-B; CELL CARCINOMA; BETA-CATENIN; GENE-EXPRESSION; TUMOR-CELLS; TARGET GENE; CANCER; TRANSCRIPTION; ONCOPROTEIN;
D O I
10.1016/j.canlet.2013.12.029
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:225 / 236
页数:12
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