ArticleCell death & disease2014
A cell-penetrating peptide based on the interaction between c-Src and connexin43 reverses glioma stem cell phenotype.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Connexin 43 C-terminus directly inhibits the hyperphosphorylation of Akt/ERK through protein-protein interactions in glioblastoma.Cancer science · 2018Pooled it
- A Convergence Model of Bioelectric, Gap Junctional, and Hippo-YAP Signalling in Oral Cancer Stem Cell Maintenance.International journal of molecular sciences · 2026Review
- Cx43 levels guide apicobasal polarity in regenerating airway epithelial cells.Communications biology · 2026Article
- Hypoxia Increases Connexin46 and Connexin43 Levels in KNS-42 Glioblastoma Cells.International journal of molecular sciences · 2026Article
- Connexin-Pannexin duality in glioblastoma.Cell and tissue research · 2026Review
- Inhibitor of DNA binding 1 in lung cancer and the tumor microenvironment: a testable hypothesis for malignant pleural effusion formation.Frontiers in immunology · 2026Review
- Injury-induced connexin 43 expression regulates endothelial wound healing.American journal of physiology. Heart and circulatory physiology · 2025Article
- Connexin 43 drives glioblastoma cancer stem cell phenotypes through a WNK lysine-deficient protein kinase 1-c-MYC signaling axis.Cell reports · 2025Article
- Connexin43 hemichannel blockade turns microglia neuroprotective and mitigates cognitive deficits in a mouse model of amyloidosis.Nature communications · 2025Article
- Review
- EGFR amplification and EGFRvIII predict and participate in TAT-Cx43266-283 antitumor response in preclinical glioblastoma models.Neuro-oncology · 2024Article
- Role of c-Src in Carcinogenesis and Drug Resistance.Cancers · 2023Review
- Connexins in Cancer, the Possible Role of Connexin46 as a Cancer Stem Cell-Determining Protein.Biomolecules · 2023Review
- The roles of connexins and gap junctions in the progression of cancer.Cell communication and signaling : CCS · 2023Review
- Connexin 43 across the Vasculature: Gap Junctions and Beyond.Journal of vascular research · 2023Review
- Src: coordinating metabolism in cancer.Oncogene · 2022Review
- Mechanisms of Connexin Regulating Peptides.International journal of molecular sciences · 2021Review
- Article
- AS602801 sensitizes glioma cells to temozolomide and vincristine by blocking gap junction communication between glioma cells and astrocytes.Journal of cellular and molecular medicine · 2021Article
- Connexin 43 peptidic medicine for glioblastoma stem cells.EBioMedicine · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Connexin43 (Cx43), the main gap junction channel-forming protein in astrocytes, is downregulated in malignant gliomas. These tumors are composed of a heterogeneous population of cells that include many with stem-cell-like properties, called glioma stem cells (GSCs), which are highly tumorigenic and lack Cx43 expression. Interestingly, restoring Cx43 reverses GSC phenotype and consequently reduces their tumorigenicity. In this study, we investigated the mechanism by which Cx43 exerts its antitumorigenic effects on GSCs. We have focused on the tyrosine kinase c-Src, which interacts with the intracellular carboxy tail of Cx43. We found that Cx43 regulates c-Src activity and proliferation in human GSCs expanded in adherent culture. Thus, restoring Cx43 in GSCs inhibited c-Src activity, which in turn promoted the downregulation of the inhibitor of differentiation Id1. Id1 sustains stem cell phenotype as it controls the expression of Sox2, responsible for stem cell self-renewal, and promotes cadherin switching, which has been associated to epithelial-mesenchymal transition. Our results show that both the ectopic expression of Cx43 and the inhibition of c-Src reduced Id1, Sox2 expression and promoted the switch from N- to E-cadherin, suggesting that Cx43, by inhibiting c-Src, downregulates Id1 with the subsequent changes in stem cell phenotype. On the basis of this mechanism, we found that a cell-penetrating peptide, containing the region of Cx43 that interacts with c-Src, mimics the effect of Cx43 on GSC phenotype, confirming the relevance of the interaction between Cx43 and c-Src in the regulation of the malignant phenotype and pinpointing this interaction as a promising therapeutic target.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.