ArticleCell death & disease2025
P2X7 a new therapeutic target to block vesicle-dependent metastasis in colon carcinoma: Role of the A2A/CD39/CD73 axis.
Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Damage-Associated Molecular Patterns in Mesothelioma: Drivers of Inflammation and Therapeutic Targets.International journal of molecular sciences · 2026Review
- Purinergic signaling in osteoarthritis: Mechanistic insights into pathogenesis and therapeutic targeting.Genes & diseases · 2026Review
- Effects on mouse melanoma and immune cells of P2X7 receptor positive allosterism by clemastine.Purinergic signalling · 2026Article
- Nucleotide signaling in neutrophils: a key player in cancer dynamics.Purinergic signalling · 2026Review
- Identification of the promoter region of the human P2RX7 gene.Purinergic signalling · 2026Article
- Review
- Methodological guidelines for P2X receptor assays and data interpretation.Cell death & disease · 2026Review
- P2X7 receptor mediates the anti-tumor effect of running on cervical cancer in mice.Purinergic signalling · 2026Article
- ATP and major affective disorders: the involvement of P2X receptors in pathophysiology.Purinergic signalling · 2026Review
- Latest advances on the role of P2X Receptors in colorectal inflammation and cancer.Purinergic signalling · 2026Review
- Hypoxic tumor microenvironment and immune cell dynamics: From metabolic reprogramming to therapeutic innovation.Iranian journal of basic medical sciences · 2026Review
Corrections and comments
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Authors and funding
14 authors.
Funding
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Abstract
Extracellular vesicle-driven cancer metastasis represents a therapeutic challenge due to the lack of effective blocking drugs. Our study shows that activation of the P2X7 receptor on colon carcinoma cells causes the release of vesicles carrying CD39 and CD73 ectonucleotidases. These vesicles increase ATP and adenosine levels and, when in vivo administered, significantly enhance colon carcinoma metastasis and circulating levels of vesicles after fourteen days from their injection. Blocking P2X7 prevents vesicular release and substantially reduces vesicle-mediated tumor spreading, positioning P2X7 as a promising therapeutic target for inhibiting extracellular vesicle-mediated dissemination in colon cancer. Additionally, these vesicles upregulate the expression of P2X7 and A2A receptors within the metastatic niche. Antagonists of P2X7 and A2A used alone or in combination effectively inhibit tumor growth in vivo, decreasing metastasis engraftment and IL-17 and IL-23 release. Interestingly, the levels of both cytokines were also reduced by combined P2X7 and A2A blockade in non-tumor-bearing mice. Moreover, P2X7 and A2A upraise in metastatic and APC-mutated colon carcinoma patients and in Apc-disrupted rats. Our findings shed light on the crosstalk of P2X7/CD73/CD39 and A2A in colon cancer metastasis. We propose a novel mechanism facilitating metastatic dissemination and an innovative therapeutic strategy to target receptor signaling and vesicular release.
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