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Connexin43 inhibits the oncogenic activity of c-Src in C6 glioma cells

Oncogene volume 29, pages 5712–5723 (2010)Cite this article

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Abstract

One of the characteristics of gliomas is a decrease in the expression of connexin43, a protein that forms gap junctions. Restoring connexin43 expression in glioma cells reduces their exacerbated rate of cell growth, although it is not yet known how connexin43 modifies the expression of genes involved in cell proliferation. Here, we show that restoring connexin43 to C6 glioma cells impedes their progression from G0/G1 to the S phase of the cell cycle by reducing retinoblastoma phosphorylation and cyclin E expression through the upregulation of p21 and p27. Interestingly, connexin43 diminishes the oncogenic activity of c-Src exhibited by glioma cells. By studying a Tyr247 and Tyr265 mutant connexin43, we show that these residues are required for connexin43 to inhibit c-Src activity and cell proliferation. In conclusion, by acting as a substrate of c-Src, connexin43 reduces its oncogenic activity and decreases the rate of glioma cell proliferation, potentially an early step in the antiproliferative effects of connexin43. Although c-Src is known to phosphorylate connexin43, this study provides the first evidence that connexin43 can also inhibit c-Src activity.

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Acknowledgements

This work was supported by the Ministerio de Educación y Ciencia, FEDER SAF2007-64161, the Junta de Castilla y León SA043A09. S Herrero-González and E Gangoso were recipient of a fellowship from the Ministerio de Educación y Ciencia. We are grateful for the technical assistance of T del Rey and we thank M Sefton for help in preparing the paper.

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Authors and Affiliations

  1. Departamento de Bioquímica y Biología Molecular, Instituto de Neurociencias de Castilla y León (INCYL), Universidad de Salamanca, Spain

    S Herrero-González, E Gangoso, J M Medina & A Tabernero

  2. INSERM U840, Collège de France, Paris, France

    C Giaume

  3. Department of Cellular and Physiological Sciences, The Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada

    C C Naus

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  1. S Herrero-González
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Correspondence to A Tabernero.

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Herrero-González, S., Gangoso, E., Giaume, C. et al. Connexin43 inhibits the oncogenic activity of c-Src in C6 glioma cells. Oncogene 29, 5712–5723 (2010). https://doi.org/10.1038/onc.2010.299

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