1. MUC1 drives epithelial–mesenchymal transition in renal carcinoma through Wnt/β-catenin pathway and interaction with SNAIL promoter
- Author
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Isabelle Van Seuningen, Sébastien Aubert, Brigitte Hémon, Christelle Cauffiez, Kelly Gaudelot, Bélinda Ringot, David Bernard, Nicolas Pottier, Arnauld Villers, Michael Perrais, David Vindrieux, Xavier Leroy, Audrey Bouillez, Viviane Gnemmi, François Glowacki, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), and Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille
- Subjects
Transcriptional Activation ,Cancer Research ,Pathology ,medicine.medical_specialty ,Epithelial-Mesenchymal Transition ,[SDV]Life Sciences [q-bio] ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Snail ,digestive system ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,biology.animal ,medicine ,Humans ,RNA, Messenger ,Epithelial–mesenchymal transition ,Promoter Regions, Genetic ,skin and connective tissue diseases ,Carcinoma, Renal Cell ,Wnt Signaling Pathway ,neoplasms ,Transcription factor ,beta Catenin ,MUC1 ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,Cell Nucleus ,0303 health sciences ,biology ,Mucin-1 ,Wnt signaling pathway ,Kidney Neoplasms ,biological factors ,digestive system diseases ,Up-Regulation ,Wnt Proteins ,HEK293 Cells ,Oncology ,030220 oncology & carcinogenesis ,Catenin ,Cancer cell ,Cancer research ,Snail Family Transcription Factors ,Signal transduction ,Transcription Factors - Abstract
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 β-catenin increased SNAIL transcriptional activity by interaction with its promoter and (v) blocking MUC1-C nuclear localization decreased Wnt/β-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.
- Published
- 2014