ArticleOncogenesis2022
Connexin 43 confers chemoresistance through activating PI3K.
Article in Oncogenesis, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- The dual role of circHIPK3 in cancer and its implications for multiple drugs resistance: a systematic review and computational approach.Frontiers in oncology · 2025Pooled it
- PIK3CB depletion restores immunosurveillance and enhances radioactive iodine response in hepatocellular carcinoma.Cell biology and toxicology · 2026Article
- E3 ligase LMO7 enhances temozolomide sensitivity by promoting MGMT degradation in lung cancer.The Journal of biological chemistry · 2026Article
- Astrocytes in neuroinflammation and brain cancer.Molecular biomedicine · 2026Review
- Connexin-Pannexin duality in glioblastoma.Cell and tissue research · 2026Review
- Beyond synapses non-synaptic neural microenvironment interactions remodel circuits and drive glioma progression.Frontiers in oncology · 2026Review
- Diverse roles of connexins in the neuro-vasculature in homeostasis and disease.Translational neuroscience · 2026Review
- Novel Cross-Cancer Hub Genes in Doxorubicin Resistance Identified by Transcriptional Mapping.Biomedicines · 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 functions as a non-canonical phenotypic stability factor in promoting hybrid Epithelial/Mesenchymal phenotype in glioblastoma cells.Translational oncology · 2025Article
- Review
- Cytoplasmic connexin43-microtubule interactions promote glioblastoma stem-like cell maintenance and tumorigenicity.Cell death & disease · 2025Article
- Glioma-astrocyte connexin43 confers temozolomide resistance through activation of the E2F1/ERCC1 axis.Neuro-oncology · 2025Article
- Tonabersat enhances temozolomide-mediated cytotoxicity in glioblastoma by disrupting intercellular connectivity through connexin 43 inhibition.Molecular oncology · 2025Article
- Review
- Molecular Basis of Oncogenic PI3K Proteins.Cancers · 2024Review
- Connexin-43 in Cancer: Above and Beyond Gap Junctions!Cancers · 2024Review
- Inhibiting lncRNA NEAT1 Increases Glioblastoma Response to TMZ by Reducing Connexin 43 Expression.Cancer reports (Hoboken, N.J.) · 2024Article
- Selective regulation of chemosensitivity in glioblastoma by phosphatidylinositol 3-kinase beta.iScience · 2024Article
- Mapping the Anti-Cancer Activity of α-Connexin Carboxyl-Terminal (aCT1) Peptide in Resistant HER2+ Breast Cancer.Cancers · 2024Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
Circumventing chemoresistance is crucial for effectively treating cancer including glioblastoma, a lethal brain cancer. The gap junction protein connexin 43 (Cx43) renders glioblastoma resistant to chemotherapy; however, targeting Cx43 is difficult because mechanisms underlying Cx43-mediated chemoresistance remain elusive. Here we report that Cx43, but not other connexins, is highly expressed in a subpopulation of glioblastoma and Cx43 mRNA levels strongly correlate with poor prognosis and chemoresistance in this population, making Cx43 the prime therapeutic target among all connexins. Depleting Cx43 or treating cells with αCT1-a Cx43 peptide inhibitor that sensitizes glioblastoma to the chemotherapy temozolomide-inactivates phosphatidylinositol-3 kinase (PI3K), whereas overexpression of Cx43 activates this signaling. Moreover, αCT1-induced chemo-sensitization is counteracted by a PI3K active mutant. Further research reveals that αCT1 inactivates PI3K without blocking the release of PI3K-activating molecules from membrane channels and that Cx43 selectively binds to the PI3K catalytic subunit β (PIK3CB, also called PI3Kβ or p110β), suggesting that Cx43 activates PIK3CB/p110β independent of its channel functions. To explore the therapeutic potential of simultaneously targeting Cx43 and PIK3CB/p110β, αCT1 is combined with TGX-221 or GSK2636771, two PIK3CB/p110β-selective inhibitors. These two different treatments synergistically inactivate PI3K and sensitize glioblastoma cells to temozolomide in vitro and in vivo. Our study has revealed novel mechanistic insights into Cx43/PI3K-mediated temozolomide resistance in glioblastoma and demonstrated that targeting Cx43 and PIK3CB/p110β together is an effective therapeutic approach for overcoming chemoresistance.
Identifiers
What Socratic holds
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 Socratic graph.