ArticleThe Journal of cell biology2020
Collective invasion induced by an autocrine purinergic loop through connexin-43 hemichannels.
Article in The Journal of cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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
28 citing papers in PubMed, 37 citations in OpenAlex.
- Imaging-Guided Live Single-Cell Lipid Profiling of Leader and Follower Cells During Collective Migration of Triple-Negative Breast Cancer Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- De Novo Gene Transcription of Connexin Mediates Cytoplasmic Fluid Exchange and Flocking Transitions in Physiological and Cancerous Epithelial Systems.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Collective migration modes in development, tissue repair and cancer.Nature reviews. Molecular cell biology · 2025Review
- Connexin hemichannel blockade by abEC1.1 disrupts glioblastoma progression, suppresses invasiveness, and reduces hyperexcitability in preclinical models.Cell communication and signaling : CCS · 2025Article
- Connexin43 Promotes the Invasion and Metastasis of Lung Squamous Cell Carcinoma via GJIC-Dependent CaCancer science · 2025Article
- Lack of canonical activities of connexins in highly aggressive human prostate cancer cells.Biological research · 2024Article
- Connexin-43 in Cancer: Above and Beyond Gap Junctions!Cancers · 2024Review
- A YAP-centered mechanotransduction loop drives collective breast cancer cell invasion.Nature communications · 2024Article
- Subpopulation commensalism promotes Rac1-dependent invasion of single cells via laminin-332.The Journal of cell biology · 2024Article
- Comprehensive Pan-Cancer Analysis of Connexin 43 as a Potential Biomarker and Therapeutic Target in Human Kidney Renal Clear Cell Carcinoma (KIRC).Medicina (Kaunas, Lithuania) · 2024Article
- Cell volume expansion and local contractility drive collective invasion of the basement membrane in breast cancer.Nature materials · 2024Article
- Review
- Revisiting 'Hallmarks of Cancer' In Sarcomas.Journal of Cancer · 2024Review
- SARS-CoV-2 spike protein S1 activates Cx43 hemichannels and disturbs intracellular CaBiological research · 2023Article
- Plasticity of cancer invasion and energy metabolism.Trends in cell biology · 2023Review
- From the Catastrophic Objective Irreproducibility of Cancer Research and Unavoidable Failures of Molecular Targeted Therapies to the Sparkling Hope of Supramolecular Targeted Strategies.International journal of molecular sciences · 2023Review
- The Multifaceted Role of Connexins in Tumor Microenvironment Initiation and Maintenance.Biology · 2023Review
- Towards targeting of shared mechanisms of cancer metastasis and therapy resistance.Nature reviews. Cancer · 2022Review
- Article
- Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
Abstract
Progression of epithelial cancers predominantly proceeds by collective invasion of cell groups with coordinated cell-cell junctions and multicellular cytoskeletal activity. Collectively invading breast cancer cells express the gap junction protein connexin-43 (Cx43), yet whether Cx43 regulates collective invasion remains unclear. We here show that Cx43 mediates gap-junctional coupling between collectively invading breast cancer cells and, via hemichannels, adenosine nucleotide/nucleoside release into the extracellular space. Using molecular interference and rescue strategies, we identify that Cx43 hemichannel function, but not intercellular communication, induces leader cell activity and collective migration through the engagement of the adenosine receptor 1 (ADORA1) and AKT signaling. Accordingly, pharmacological inhibition of ADORA1 or AKT signaling caused leader cell collapse and halted collective invasion. ADORA1 inhibition further reduced local invasion of orthotopic mammary tumors in vivo, and joint up-regulation of Cx43 and ADORA1 in breast cancer patients correlated with decreased relapse-free survival. This identifies autocrine purinergic signaling, through Cx43 hemichannels, as a critical pathway in leader cell function and collective invasion.
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What OpenQuestion 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 OpenQuestion graph.