ArticleScientific reports2016
Activation of P2X7 and P2Y11 purinergic receptors inhibits migration and normalizes tumor-derived endothelial cells via cAMP signaling.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 68 citations in OpenAlex.
- Article
- Role of the P2X7 receptor in breast cancer progression.Purinergic signalling · 2025Review
- Functional role of P2X7 purinergic receptor in cancer and cancer-related pain.Purinergic signalling · 2025Review
- Purinergic pathways and their clinical use in the treatment of acute myeloid leukemia.Purinergic signalling · 2025Review
- Novel synthesized ionizable lipid for LNP-mediated P2X7siRNA to inhibit migration and induce apoptosis of breast cancer cells.Purinergic signalling · 2024Article
- Purine and purinergic receptors in health and disease.MedComm · 2023Review
- Spotlight on P2X7 Receptor PET Imaging: A Bright Target or a Failing Star?International journal of molecular sciences · 2023Review
- The ATP-dependent Pathways and Human Diseases.Current medicinal chemistry · 2023Article
- GαBiomolecules · 2022Article
- Transient Receptor Potential (TRP) Channels in Tumor Vascularization.International journal of molecular sciences · 2022Review
- The P2YCellular and molecular life sciences : CMLS · 2022Article
- Article
- The Role of Purinergic P2X7 Receptor in Inflammation and Cancer: Novel Molecular Insights and Clinical Applications.Cancers · 2022Review
- Potentiating Cancer Immune TherapyFrontiers in cell and developmental biology · 2022Article
- Calcium-Permeable Channels in Tumor Vascularization: Peculiar Sensors of Microenvironmental Chemical and Physical Cues.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Extracellular ATP Induced S-Phase Cell Cycle Arrest via P2Y Receptor-Activated ERK Signaling in Poorly Differentiated Oral Squamous Cell Carcinoma SAS Cells.Life (Basel, Switzerland) · 2021Article
- LPHN2 inhibits vascular permeability by differential control of endothelial cell adhesion.The Journal of cell biology · 2021Article
- Autocrine and paracrine purinergic signaling in the most lethal types of cancer.Purinergic signalling · 2021Review
- ATP Inhibits Breast Cancer Migration and Bone Metastasis through Down-Regulation of CXCR4 and Purinergic Receptor P2Y11.Cancers · 2021Article
- Advances in Intracellular Calcium Signaling Reveal Untapped Targets for Cancer Therapy.Biomedicines · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purinergic signaling is involved in inflammation and cancer. Extracellular ATP accumulates in tumor interstitium, reaching hundreds micromolar concentrations, but its functional role on tumor vasculature and endothelium is unknown. Here we show that high ATP doses (>20 μM) strongly inhibit migration of endothelial cells from human breast carcinoma (BTEC), but not of normal human microvascular EC. Lower doses (1-10 μM result ineffective. The anti-migratory activity is associated with cytoskeleton remodeling and is significantly prevented by hypoxia. Pharmacological and molecular evidences suggest a major role for P2X7R and P2Y11R in ATP-mediated inhibition of TEC migration: selective activation of these purinergic receptors by BzATP mimics the anti-migratory effect of ATP, which is in turn impaired by their pharmacological or molecular silencing. Downstream pathway includes calcium-dependent Adenilyl Cyclase 10 (AC10) recruitment, cAMP release and EPAC-1 activation. Notably, high ATP enhances TEC-mediated attraction of human pericytes, leading to a decrease of endothelial permeability, a hallmark of vessel normalization. Finally, we provide the first evidence of in vivo P2X7R expression in blood vessels of murine and human breast carcinoma. In conclusion, we have identified a purinergic pathway selectively acting as an antiangiogenic and normalizing signal for human tumor-derived vascular endothelium.
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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.