title: Connexin 32 and its derived homotypic gap junctional intercellular communication inhibit the migration and invasion of transfected HeLa cells via enhancement of intercellular adhesion.
abstract: The effects of connexin (Cx) and its derived homotypic gap junctional intercellular communication (GJIC) between tumor cells on the invasion of metastatic cancers and the underlying mechanisms remain unclear. In this study, we investigated the influence of Cx32 and the homotypic GJIC mediated by this Cx on the migration, invasion and intercellular adhesion of transfected HeLa cells. The expression of Cx32 significantly increased cell adhesion and inhibited migration and invasion. The inhibition of GJIC by oleamide, a widely used GJIC inhibitor, reduced the enhanced adhesion and partly reversed the decreased migration and invasion that had been induced by Cx32 expression. Blockage of the p38 and extracellular signal-regulated kinase 1 and 2 mitogen-activated protein kinase (ERK1/2 MAPKs) pathways using their specific inhibitors attenuated the effects of Cx32, but not those of GJIC, on cell adhesion, migration and invasion. These results indicate that the homotypic GJIC mediated by Cx32, as well as the Cx itself, inhibit cell migration and invasion, most likely through the elevation of intercellular adhesion. The suppressive effect of Cx32 on the migration and invasion of cancer cells, but not that of its derived homotypic GJIC, partly depends on the activation of the p38 and the ERK1/2 MAPKs pathways.
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Dongdong
authors.initials: D
authors.lastname: Yuan
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Hong
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Liang
authors.initials: L
authors.lastname: Tao
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D017630:Connexins / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009361:Neoplasm Invasiveness; D009829:Oleic Acids / Q000494:pharmacology; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D048049:Extracellular Signal-Regulated MAP Kinases; D009829:Oleic Acids; D048051:p38 Mitogen-Activated Protein Kinases; D000097002:Gap Junction beta-1 Protein; C029407:oleylamide