Overexpression of connexin 43 reduces melanoma proliferative and metastatic capacity

Background: 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 capabi...

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Published in:British journal of cancer 2015-07, Vol.113 (2), p.259-267
Main Authors: Tittarelli, A, Guerrero, I, Tempio, F, Gleisner, M A, Avalos, I, Sabanegh, S, Ortíz, C, Michea, L, López, M N, Mendoza-Naranjo, A, Salazar-Onfray, F
Format: Article
Language:English
Subjects:
631/67/322
692/420/2489/144
692/699/67/1059
692/699/67/1813/1634
Animals
Apoptosis
Biomedical and Life Sciences
Biomedicine
Calcium - metabolism
Cancer Research
Cell Communication
Cell Line, Tumor
Cell Proliferation
Connexin 43 - physiology
Drug Resistance
Epidemiology
Gap Junctions - physiology
Humans
Melanoma - pathology
Melanoma - secondary
Mice
Mice, Inbred NOD
Molecular Diagnostics
Molecular Medicine
Neoplasm Metastasis
Oncology
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Summary:Background: 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 . Methods: 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. Results: 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 . Conclusions: 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.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2015.162