title: The MUC1 oncomucin regulates pancreatic cancer cell biological properties and chemoresistance. Implication of p42-44 MAPK, Akt, Bcl-2 and MMP13 pathways.
abstract: MUC1 is an oncogenic mucin overexpressed in several epithelial cancers, including pancreatic ductal adenocarcinoma, and is considered as a potent target for cancer therapy. To this aim, we undertook to study MUC1 biological effects on pancreatic cancer cells and identify pathways mediating these effects. Our in vitro experiments indicate that inhibiting MUC1 expression decreases cell proliferation, cell migration and invasion, cell survival and increases cell apoptosis. Moreover, lack of MUC1 in these cells profoundly altered their sensitivity to gemcitabine and 5-Fluorouracil chemotherapeutic drugs. In vivo MUC1-KD cell xenografts in SCID mice grew slower. Altogether, we show that MUC1 oncogenic mucin alters proliferation, migration, and invasion properties of pancreatic cancer cells and that these effects are mediated by p42-44 MAPK, Akt, Bcl-2 and MMP13 pathways.
authors.affiliation: Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 "Mucins, Epithelial Differentiation and Carcinogenesis", Rue Polonovski, 59045 Lille Cedex, France; Université de Lille 2, 42 rue Paul Duez, 59000 Lille, France; Centre Hospitalier Régional et Universitaire de Lille, 59037 Lille Cedex, France.
authors.forename: Solange
authors.initials: S
authors.lastname: Tréhoux
authors.affiliation: Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 "Mucins, Epithelial Differentiation and Carcinogenesis", Rue Polonovski, 59045 Lille Cedex, France; Université de Lille 2, 42 rue Paul Duez, 59000 Lille, France; Centre Hospitalier Régional et Universitaire de Lille, 59037 Lille Cedex, France.
authors.forename: Bélinda
authors.initials: B
authors.lastname: Duchêne
authors.affiliation: Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 "Mucins, Epithelial Differentiation and Carcinogenesis", Rue Polonovski, 59045 Lille Cedex, France; Université de Lille 2, 42 rue Paul Duez, 59000 Lille, France; Centre Hospitalier Régional et Universitaire de Lille, 59037 Lille Cedex, 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", Rue Polonovski, 59045 Lille Cedex, France; Université de Lille 2, 42 rue Paul Duez, 59000 Lille, France; Centre Hospitalier Régional et Universitaire de Lille, 59037 Lille Cedex, France. Electronic address: isabelle.vanseuningen@inserm.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Van Seuningen
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000502:physiology*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D018396:Mucin-1 / Q000235:genetics / Q000502:physiology*; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt; D000093542:Gemcitabine
chemical_list: D000951:Antigens, Neoplasm; D000964:Antimetabolites, Antineoplastic; C060192:MUC1 protein, human; D018396:Mucin-1; D003841:Deoxycytidine; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053509:Matrix Metalloproteinase 13; D005472:Fluorouracil; D000093542:Gemcitabine
keywords: Chemoresistance; Invasion; MUC1; Migration; Pancreatic cancer; Proliferation