title: MUC1 drives epithelial-mesenchymal transition in renal carcinoma through Wnt/β-catenin pathway and interaction with SNAIL promoter.
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.
authors.affiliation: Institut 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.
authors.forename: Viviane
authors.initials: V
authors.lastname: Gnemmi
authors.affiliation: Institut 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.
authors.forename: Audrey
authors.initials: A
authors.lastname: Bouillez
authors.affiliation: Institut 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.
authors.forename: Kelly
authors.initials: K
authors.lastname: Gaudelot
authors.affiliation: Institut 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.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Hémon
authors.affiliation: Institut 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.
authors.forename: Bélinda
authors.initials: B
authors.lastname: Ringot
authors.affiliation: Faculté 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.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pottier
authors.affiliation: Faculté 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.
authors.forename: François
authors.initials: F
authors.lastname: Glowacki
authors.affiliation: Faculté 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.
authors.forename: Arnauld
authors.initials: A
authors.lastname: Villers
authors.affiliation: UMR CNRS 5286/INSERM 1052, Centre de Recherche en Cancérologie de Lyon, France.
authors.forename: David
authors.initials: D
authors.lastname: Vindrieux
authors.affiliation: Faculté 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.
authors.forename: Christelle
authors.initials: C
authors.lastname: Cauffiez
authors.affiliation: Institut 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.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Van Seuningen
authors.affiliation: UMR CNRS 5286/INSERM 1052, Centre de Recherche en Cancérologie de Lyon, France.
authors.forename: David
authors.initials: D
authors.lastname: Bernard
authors.affiliation: Institut 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.
authors.forename: Xavier
authors.initials: X
authors.lastname: Leroy
authors.affiliation: Institut 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.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Aubert
authors.affiliation: Institut 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.
authors.forename: Michaël
authors.initials: M
authors.lastname: Perrais
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D057809:HEK293 Cells; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018396:Mucin-1 / Q000096:biosynthesis* / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015533:Transcriptional Activation; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; C060192:MUC1 protein, human; D018396:Mucin-1; D012333:RNA, Messenger; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin
keywords: Beta catenin; Epithelial mesenchymal transition; GO-203; MUC1; SNAIL