ArticleInternational journal of molecular sciences2020
Inhibiting P2Y12 in Macrophages Induces Endoplasmic Reticulum Stress and Promotes an Anti-Tumoral Phenotype.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Platelets: the first cellular responders in the foreign body response to blood-contacting biomaterials.Frontiers in immunology · 2026Review
- Co-treatment of ticagrelor and anti-PD-1 immunotherapy in tumor-associated macrophages reduces pancreatic cancer cell growth and migration through the TGF-β1/Smad2 pathway.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Macrophage P2Y12 regulates iron transport and its inhibition protects against atherosclerosis.Journal of advanced research · 2025Article
- Role and recent progress of P2Y12 receptor in cancer development.Purinergic signalling · 2025Review
- P2Y12 receptor-mediated cyclooxygenase 2 (COX-2) expression enhances tumor cell progression in a mouse model of lymphoma.Purinergic signalling · 2025Article
- P2 purinergic receptor expression and function in tumor-related immune cells.Purinergic signalling · 2025Review
- Ticagrelor inhibits the growth of lung adenocarcinoma by downregulating SYK expression and modulating the PI3K/AKT pathway.Scientific reports · 2025Article
- Clopidogrel protects against gentamicin-induced nephrotoxicity through targeting oxidative stress, apoptosis, and coagulation pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Sex-specific activation of platelet purinergic signaling is key in local cytokine release and phagocytosis in the peritoneal cavity in intra-abdominal sepsis.American journal of physiology. Cell physiology · 2025Article
- Gastrointestinal side effects in hepatocellular carcinoma patients receiving transarterial chemoembolization: a meta-analysis of 81 studies and 9495 patients.Therapeutic advances in medical oncology · 2025Article
- The ion transport, GPCR, and RTK toolkit expression in the human cerebrovascular endothelial cell line, hCMEC/D3: an Omics perspective.Frontiers in physiology · 2025Article
- Sustainable Immunomodulatory via Macrophage P2Y12 Inhibition Mediated Bioactive Patche for Peritendinous Antiadhesion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Predictive three-biomarker panel in peripheral blood mononuclear cells for detecting hepatocellular carcinoma.Scientific reports · 2024Article
- The Signaling Pathway of the ADP Receptor P2YInternational journal of molecular sciences · 2023Review
- A role for platelets in metabolic reprogramming of tumor-associated macrophages.Frontiers in physiology · 2023Review
- P2Y12 inhibitor clopidogrel inhibits renal fibrosis by blocking macrophage-to-myofibroblast transition.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Review
- Sex-related differences in the response of anti-platelet drug therapies targeting purinergic signaling pathways in sepsis.Frontiers in immunology · 2022Article
- Review
- Exploring the Role of Endoplasmic Reticulum Stress in Hepatocellular Carcinoma through mining of the Human Protein Atlas.Biology · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The P2Y12 receptor is an adenosine diphosphate responsive G protein-coupled receptor expressed on the surface of platelets and is the pharmacologic target of several anti-thrombotic agents. In this study, we use liver samples from mice with cirrhosis and hepatocellular carcinoma to show that P2Y12 is expressed by macrophages in the liver. Using in vitro methods, we show that inhibition of P2Y12 with ticagrelor enhances tumor cell phagocytosis by macrophages and induces an anti-tumoral phenotype. Treatment with ticagrelor also increases the expression of several actors of the endoplasmic reticulum (ER) stress pathways, suggesting activation of the unfolded protein response (UPR). Inhibiting the UPR with tauroursodeoxycholic acid (Tudca) diminishes the pro-phagocytotic effect of ticagrelor, thereby indicating that P2Y12 mediates macrophage function through activation of ER stress pathways. This could be relevant in the pathogenesis of chronic liver disease and cancer, as macrophages are considered key players in these inflammation-driven pathologies.
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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.