title: The MUC1 mucin regulates the tumorigenic properties of human esophageal adenocarcinomatous cells.
abstract: MUC1 is a membrane-bound mucin known to participate in tumor proliferation. It has been shown that MUC1 pattern of expression is modified during esophageal carcinogenesis, with a progressive increase from metaplasia to adenocarcinoma. The principal cause of development of esophageal adenocarcinoma is gastro-esophageal reflux and MUC1 was previously shown to be up-regulated by several bile acids present in reflux. In this report, our aim was thus to determine whether MUC1 plays a role in biological properties of human esophageal cancer cells. For that, a stable MUC1-deficient esophageal cancer cell line was established using a shRNA approach. In vitro (proliferation, migration and invasion) and in vivo (tumor growth following subcutaneous xenografts in SCID mice) biological properties of MUC1-deficient cells were analyzed. Our results show that esophageal cancer cells lacking MUC1 were less proliferative and had decreased migration and invasion properties. These alterations were accompanied by a decreased activity of NFKB p65, Akt and MAPK (p44/42, JNK and p38) pathways. MCM6 and TSG101 tumor-associated markers were also decreased. Subcutaneous xenografts showed a significant decrease in tumor size when cells did not express MUC1. Altogether, the data indicate that MUC1 plays a key role in proliferative, migrating and invasive properties of esophageal cancer cells as well as in tumor growth promotion. MUC1 mucin appears thus as a good therapeutic target to slow down esophageal tumor progression.
authors.affiliation: Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 "Mucins, Epithelial Differentiation and Carcinogenesis", Lille, France; Université Lille-Nord de France, Lille, France; Department of Digestive and Oncological Surgery, University Hospital Claude Huriez, Lille, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Gronnier
authors.affiliation: Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 "Mucins, Epithelial Differentiation and Carcinogenesis", Lille, France; Université Lille-Nord de France, Lille, France; Department of Digestive and Oncological Surgery, University Hospital Claude Huriez, Lille, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Bruyère
authors.affiliation: Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 "Mucins, Epithelial Differentiation and Carcinogenesis", Lille, France; Université Lille-Nord de France, Lille, France; Department of Digestive and Oncological Surgery, University Hospital Claude Huriez, Lille, France.
authors.forename: Fatima
authors.initials: F
authors.lastname: Lahdaoui
authors.affiliation: Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 "Mucins, Epithelial Differentiation and Carcinogenesis", Lille, France; Université Lille-Nord de France, Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Jonckheere
authors.affiliation: Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 "Mucins, Epithelial Differentiation and Carcinogenesis", Lille, France; Université Lille-Nord de France, Lille, France.
authors.forename: Michaël
authors.initials: M
authors.lastname: Perrais
authors.affiliation: Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 "Mucins, Epithelial Differentiation and Carcinogenesis", Lille, France; Université Lille-Nord de France, Lille, France; Centre de Biologie-Pathologie, Department of Pathology, Centre Hospitalier Régional et Universitaire, Lille, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Leteurtre
authors.affiliation: Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 "Mucins, Epithelial Differentiation and Carcinogenesis", Lille, France; Université Lille-Nord de France, Lille, France; Department of Digestive and Oncological Surgery, University Hospital Claude Huriez, Lille, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Piessen
authors.affiliation: Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 "Mucins, Epithelial Differentiation and Carcinogenesis", Lille, France; Université Lille-Nord de France, Lille, France; Department of Digestive and Oncological Surgery, University Hospital Claude Huriez, Lille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Mariette
authors.affiliation: Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 "Mucins, Epithelial Differentiation and Carcinogenesis", Lille, France; Université Lille-Nord de France, Lille, France. Electronic address: isabelle.vanseuningen@inserm.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Van Seuningen
keywords: Adenocarcinoma; Esophagus; Invasion; MUC1; Mucin; Proliferation