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Cancer Lett. 2014 May 1;346(2):225-36. doi: 10.1016/j.canlet.2013.12.029. Epub 2013 Dec 30.

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

Author information

  • 1Institut National de la Santé et de la Recherche Médicale (Inserm), UMR837, Equipe 5 "Mucines, différenciation et cancérogenèse épithéliales", Jean-Pierre Aubert Research Center, Rue Michel Polonovski, 59045 Lille Cedex, France; Institute of Pathology, Centre de Biologie-Pathologie, CHRU de Lille, 2 avenue Oscar Lambret, 59037 Lille Cedex, France; Faculté de Médecine Henri-Warembourg, Université de Lille 2, F-59045 Lille, France. Electronic address: viviane.gnemmi@inserm.fr.
  • 2Institut National de la Santé et de la Recherche Médicale (Inserm), UMR837, Equipe 5 "Mucines, différenciation et cancérogenèse épithéliales", Jean-Pierre Aubert Research Center, Rue Michel Polonovski, 59045 Lille Cedex, France.
  • 3Faculté de Médecine Henri-Warembourg, Université de Lille 2, F-59045 Lille, France; EA4483, Department of Biochemistry and Molecular Biology, Faculté de Médecine, Pôle Recherche, Place de Verdun, 59045 Lille, France.
  • 4Faculté de Médecine Henri-Warembourg, Université de Lille 2, F-59045 Lille, France; EA4483, Department of Biochemistry and Molecular Biology, Faculté de Médecine, Pôle Recherche, Place de Verdun, 59045 Lille, France; Department of Nephrology, Hôpital Huriez, CHRU de Lille, Rue Michel Polonovski, 59037 Lille Cedex, France.
  • 5Faculté de Médecine Henri-Warembourg, Université de Lille 2, F-59045 Lille, France; Department of Urology, Hopital Huriez, CHRU de Lille, Rue Michel Polonovski, 59037 Lille Cedex, France.
  • 6UMR CNRS 5286/INSERM 1052, Centre de Recherche en Cancérologie de Lyon, France.
  • 7Institut National de la Santé et de la Recherche Médicale (Inserm), UMR837, Equipe 5 "Mucines, différenciation et cancérogenèse épithéliales", Jean-Pierre Aubert Research Center, Rue Michel Polonovski, 59045 Lille Cedex, France; Institute of Pathology, Centre de Biologie-Pathologie, CHRU de Lille, 2 avenue Oscar Lambret, 59037 Lille Cedex, France; Faculté de Médecine Henri-Warembourg, Université de Lille 2, F-59045 Lille, France.
  • 8Institut National de la Santé et de la Recherche Médicale (Inserm), UMR837, Equipe 5 "Mucines, différenciation et cancérogenèse épithéliales", Jean-Pierre Aubert Research Center, Rue Michel Polonovski, 59045 Lille Cedex, France; Faculté de Médecine Henri-Warembourg, Université de Lille 2, F-59045 Lille, France.

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.

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

KEYWORDS:

Beta catenin; Epithelial mesenchymal transition; GO-203; MUC1; SNAIL

PMID:
24384091
[PubMed - indexed for MEDLINE]
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