title: Overexpression of connexin 43 reduces melanoma proliferative and metastatic capacity.
abstract: Alterations in connexin 43 (Cx43) expression and/or gap junction (GJ)-mediated intercellular communication are implicated in cancer pathogenesis. Herein, we have investigated the role of Cx43 in melanoma cell proliferation and apoptosis sensitivity in vitro, as well as metastatic capability and tumour growth in vivo.
  
  
  
  Connexin 43 expression levels, GJ coupling and proliferation rates were analysed in four different human melanoma cell lines. Furthermore, tumour growth and lung metastasis of high compared with low Cx43-expressing FMS cells were evaluated in vivo using a melanoma xenograft model.
  
  
  
  Specific inhibition of Cx43 channel activity accelerated melanoma cell proliferation, whereas overexpression of Cx43 increased GJ coupling and reduced cell growth. Moreover, Cx43 overexpression in FMS cells increased basal and tumour necrosis factor-α-induced apoptosis and resulted in decreased melanoma tumour growth and lower number and size of metastatic foci in vivo.
  
  
  
  Our findings reveal an important role for Cx43 in intrinsically controlling melanoma growth, death and metastasis, and emphasise the potential use of compounds that selectively enhance Cx43 expression on melanoma in the future chemotherapy and/or immunotherapy protocols.
authors.affiliation: Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 8380453, Chile.
authors.forename: A
authors.initials: A
authors.lastname: Tittarelli
authors.affiliation: Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 8380453, Chile.
authors.forename: I
authors.initials: I
authors.lastname: Guerrero
authors.affiliation: 1] Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 8380453, Chile [2] Millennium Institute on Immunology and Immunotherapy, Institute of Biomedical Sciences, University of Chile, Santiago 8380453, Chile.
authors.forename: F
authors.initials: F
authors.lastname: Tempio
authors.affiliation: Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 8380453, Chile.
authors.forename: M A
authors.initials: MA
authors.lastname: Gleisner
authors.affiliation: Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 8380453, Chile.
authors.forename: I
authors.initials: I
authors.lastname: Avalos
authors.affiliation: Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 8380453, Chile.
authors.forename: S
authors.initials: S
authors.lastname: Sabanegh
authors.affiliation: Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 8380453, Chile.
authors.forename: C
authors.initials: C
authors.lastname: Ortíz
authors.affiliation: 1] Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 8380453, Chile [2] Millennium Institute on Immunology and Immunotherapy, Institute of Biomedical Sciences, University of Chile, Santiago 8380453, Chile.
authors.forename: L
authors.initials: L
authors.lastname: Michea
authors.affiliation: 1] Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 8380453, Chile [2] Millennium Institute on Immunology and Immunotherapy, Institute of Biomedical Sciences, University of Chile, Santiago 8380453, Chile [3] Research Support Office, University of Chile Clinical Hospital, Santiago 8380453, Chile.
authors.forename: M N
authors.initials: MN
authors.lastname: López
authors.affiliation: UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6DD, UK.
authors.forename: A
authors.initials: A
authors.lastname: Mendoza-Naranjo
authors.affiliation: 1] Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 8380453, Chile [2] Millennium Institute on Immunology and Immunotherapy, Institute of Biomedical Sciences, University of Chile, Santiago 8380453, Chile.
authors.forename: F
authors.initials: F
authors.lastname: Salazar-Onfray
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018031:Connexin 43 / Q000502:physiology*; D017629:Gap Junctions / Q000502:physiology; D006801:Humans; D008545:Melanoma / Q000473:pathology* / Q000556:secondary; D051379:Mice; D016688:Mice, Inbred NOD; D009362:Neoplasm Metastasis
chemical_list: D018031:Connexin 43; D002118:Calcium