title: The MUC4 membrane-bound mucin regulates esophageal cancer cell proliferation and migration properties: Implication for S100A4 protein.
abstract: MUC4 is a membrane-bound mucin known to participate in tumor progression. It has been shown that MUC4 pattern of expression is modified during esophageal carcinogenesis, with a progressive increase from metaplastic lesions to adenocarcinoma. The principal cause of development of esophageal adenocarcinoma is the gastro-esophageal reflux, and MUC4 was previously shown to be upregulated by several bile acids present in reflux. In this report, our aim was thus to determine whether MUC4 plays a role in biological properties of human esophageal cancer cells. For that stable MUC4-deficient cancer cell lines (shMUC4 cells) were 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 shMUC4 cells were analyzed. Our results show that shMUC4 cells were less proliferative, had decreased migration properties and did not express S100A4 protein when compared with MUC4 expressing cells. Absence of MUC4 did not impair shMUC4 invasiveness. Subcutaneous xenografts showed a significant decrease in tumor size when cells did not express MUC4. Altogether, these data indicate that MUC4 plays a key role in proliferative and migrating properties of esophageal cancer cells as well as is a tumor growth promoter. MUC4 mucin appears thus as a good therapeutic target to slow-down esophageal tumor progression.
authors: Inserm, UMR837, Jean-Pierre Aubert Research Center, Team 5 Mucins, Epithelial Differentiation and Carcinogenesis, rue Polonovski, 59045 Lille Cedex, France.
authors: Emilie
authors: E
authors: Bruyère
authors: Nicolas
authors: N
authors: Jonckheere
authors: Frédéric
authors: F
authors: Frénois
authors: Christophe
authors: C
authors: Mariette
authors: Isabelle
authors: I
authors: Van Seuningen
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D055264:Mucin-4 / Q000235:genetics / Q000502:physiology*; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000235:genetics; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays
chemical_list: C524658:MUC4 protein, human; D055264:Mucin-4; D034741:RNA, Small Interfering; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human