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

TitleConnexin43 inhibits the oncogenic activity of c-Src in C6 glioma cells.
Publication TypeJournal Article
Year of Publication2010
AuthorsHerrero-González S, Gangoso E, Giaume C, Naus CC, Medina JM, Tabernero A
JournalOncogene
Volume29
Issue42
Pagination5712-23
Date Published2010 Oct 21
ISSN1476-5594
KeywordsAnimals, Blotting, Western, Cell Cycle, Cell Line, Tumor, Cell Proliferation, Cell Separation, Connexin 43, Flow Cytometry, Gene Expression, Gene Expression Regulation, Neoplastic, Genes, src, Glioma, Mutation, Rats, RNA, Small Interfering, Transfection
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.

DOI10.1038/onc.2010.299
Alternate JournalOncogene
PubMed ID20676131
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