Related Experiment Video
Updated: Jun 10, 2026
Biotinylated Cell-penetrating Peptides to Study Intracellular Protein-protein Interactions
Published on: December 20, 2017
Connexin43 inhibits the oncogenic activity of c-Src in C6 glioma cells
S Herrero-González1, E Gangoso, C Giaume
1Departamento de Bioquímica y Biología Molecular, Instituto de Neurociencias de Castilla y León, Universidad de Salamanca, Spain.
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.
Insights
Restoring connexin43 (a gap junction protein) in glioma cells inhibits cell proliferation by downregulating cell cycle progression and reducing the oncogenic activity of c-Src. This study reveals connexin43 acts as a substrate to inhibit c-Src, impacting glioma growth.
Area of Science:
- Neuro-oncology
- Cell Biology
- Molecular Biology
Background:
- Gliomas exhibit reduced connexin43 expression, a gap junction protein.
- The mechanism by which connexin43 influences glioma cell proliferation remains unclear.
Purpose of the Study:
- To elucidate how restoring connexin43 expression affects glioma cell cycle progression and oncogenic signaling.
- To investigate the role of specific connexin43 residues in inhibiting c-Src activity and cell proliferation.
Main Methods:
- Utilized C6 glioma cells with restored connexin43 expression.
- Analyzed cell cycle progression, retinoblastoma phosphorylation, and expression of cyclins (E) and inhibitors (p21, p27).
- Employed Tyr247 and Tyr265 mutant connexin43 to assess functional domains.
Main Results:
- Connexin43 restoration impeded G0/G1 to S phase transition by upregulating p21/p27 and reducing retinoblastoma phosphorylation and cyclin E.
- Connexin43 significantly diminished the oncogenic activity of c-Src in glioma cells.
- Specific tyrosine residues (Tyr247, Tyr265) in connexin43 are crucial for inhibiting c-Src activity and cell proliferation.
Conclusions:
- Connexin43 acts as a substrate for c-Src, thereby inhibiting its oncogenic activity and reducing glioma cell proliferation.
- This interaction represents a potential early mechanism for connexin43's antiproliferative effects in gliomas.
- Provides the first evidence of connexin43 inhibiting c-Src activity, complementing known phosphorylation interactions.
Related Concept Videos
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:03Rous Sarcoma Virus (RSV) and Cancer
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...