title: Regulation of membrane-type 1 matrix metalloproteinase expression by zonula occludens-2 in human lung cancer cells.
abstract: During tumor invasion, tumor epithelial cells acquire migratory and invasive properties involving important phenotypic alterations. Among these changes, one can observe reorganization or a loss of cell-cell adhesion complexes such as tight junctions (TJs). TJs are composed of transmembrane proteins (occludin, claudins) linked to the actin cytoskeleton through cytoplasmic adaptor molecules including those of the zonula occludens family (ZO-1, -2, -3). We here evaluated the potential role of ZO-2 in the acquisition of invasive properties by tumor cells. In vivo, we showed a decrease of ZO-2 expression in bronchopulmonary cancers, with a preferential localization in the cytoplasm. In addition, in vitro, the localization of ZO-2 varied according to invasive properties of tumor cells, with a cytoplasmic localization correlating with invasion. In addition, we demonstrated that ZO-2 inhibition increases invasive and migrative capacities of invasive tumor cells. This was associated with an increase of MT1-MMP. These results suggest that ZO-2, besides its structural role in tight junction assembly, can act also as a repressor of tumor progression through its ability to reduce the expression of tumor-promoting genes in invasive tumor cells.
authors.affiliation: INSERM UMR-S 903, SFR CAP-SANTE FED 4231, University of Reims-Champagne-Ardenne, 45, rue Cognacq-Jay, 51100, Reims, France.
authors.forename: E
authors.initials: E
authors.lastname: Luczka
authors.forename: L
authors.initials: L
authors.lastname: Syne
authors.forename: B
authors.initials: B
authors.lastname: Nawrocki-Raby
authors.forename: C
authors.initials: C
authors.lastname: Kileztky
authors.forename: W
authors.initials: W
authors.lastname: Hunziker
authors.forename: P
authors.initials: P
authors.lastname: Birembaut
authors.forename: C
authors.initials: C
authors.lastname: Gilles
authors.forename: Myriam
authors.initials: M
authors.lastname: Polette
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome; D062827:Zonula Occludens-2 Protein / Q000502:physiology*
chemical_list: D017931:DNA Primers; D034741:RNA, Small Interfering; C569046:TJP2 protein, human; D062827:Zonula Occludens-2 Protein; D053511:Matrix Metalloproteinase 14