ArticleAmerican journal of respiratory and critical care medicine2012
Receptor of activated protein C promotes metastasis and correlates with clinical outcome in lung adenocarcinoma.
Article in American journal of respiratory and critical care medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 56 citations in OpenAlex.
- Activated protein C promotes human lung cancer progression through the release of tumor extracellular vesicles and transfer of microRNA-200a.Cell death & disease · 2025Article
- Endothelial Protein C Receptor: A Multifunctional Mediator in the Pathophysiology of Rheumatoid Arthritis.Cells · 2025Review
- Endothelial Protein C Receptor and Its Impact on Rheumatic Disease.Journal of clinical medicine · 2024Review
- EPCR deficiency ameliorates inflammatory arthritis in mice by suppressing the activation and migration of T cells and dendritic cells.Rheumatology (Oxford, England) · 2024Article
- Exploring the association between circulating endothelial protein C receptor and disease activity of rheumatoid arthritis in a pilot study.Rheumatology advances in practice · 2024Article
- A Bibliometric and In Silico-Based Analysis of Anti-Lung Cancer Compounds from Sea Cucumber.Marine drugs · 2023Review
- Chemical Compositions and Experimental and Computational Modeling of the Anticancer Effects of Cnidocyte Venoms of JellyfishMarine drugs · 2023Article
- New insights into vitamin K biology with relevance to cancer.Trends in molecular medicine · 2022Review
- CircTUBGCP3 facilitates the tumorigenesis of lung adenocarcinoma by sponging miR-885-3p.Cancer cell international · 2021Article
- Down-regulation of endothelial protein C receptor promotes preeclampsia by affecting actin polymerization.Journal of cellular and molecular medicine · 2020Article
- Review
- EPCR promotes MGC803 human gastric cancer cell tumor angiogenesisOncology letters · 2018Article
- Endothelial cell protein C receptor-dependent signaling.Current opinion in hematology · 2018Review
- Blockade of the Complement C5a/C5aR1 Axis Impairs Lung Cancer Bone Metastasis by CXCL16-mediated Effects.American journal of respiratory and critical care medicine · 2018Article
- Protein C receptor stimulates multiple signaling pathways in breast cancer cells.The Journal of biological chemistry · 2018Article
- TR47, a PAR1-based peptide, inhibits melanoma cell migration in vitro and metastasis in vivo.Biochemical and biophysical research communications · 2018Article
- Endothelial protein C receptor is overexpressed in colorectal cancer as a result of amplification and hypomethylation of chromosome 20q.The journal of pathology. Clinical research · 2017Article
- Endothelial protein C receptor polymorphisms and risk of sepsis in a Chinese population.The Journal of international medical research · 2017Article
- EPCR promotes breast cancer progression by altering SPOCK1/testican 1-mediated 3D growth.Journal of hematology & oncology · 2017Article
- Intrapleural Adenoviral-mediated Endothelial Cell Protein C Receptor Gene Transfer Suppresses the Progression of Malignant Pleural Mesothelioma in a Mouse Model.Scientific reports · 2016Article
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16 authors at 5 institutions in 4 countries.
Funding
Abstract
rationaleEfficient metastasis requires survival and adaptation of tumor cells to stringent conditions imposed by the extracellular milieu. Identification of critical survival signaling pathways in tumor cells might unveil novel targets relevant in disease progression.
objectivesTo investigate the contribution of activated protein C (APC) and its receptor (endothelial protein C receptor [EPCR]) in animal models of lung cancer metastasis and in patients with lung adenocarcinoma.
methodsSignaling pathway triggered by APC/EPCR and its relevance in apoptosis was studied in vitro. Functional significance was assessed by silencing and blocking antibodies in several in vivo models of lung cancer metastasis in athymic nude Foxn1(nu) mice. We examined EPCR levels using a microarray dataset of 107 patients. Immunohistochemical analysis was performed in an independent cohort of 295 patients with lung adenocarcinoma. MEASUREMENTS AND MAIN
resultsThe effects of APC binding to EPCR rapidly triggered Akt and extracellular signal-regulated kinase signaling pathways, leading to attenuated in vitro apoptosis. In vivo, silencing of EPCR expression or blocking APC/EPCR interaction reduced infiltration in the target organ, resulting in impaired prometastatic activity. Moreover, overexpression of EPCR induced an increased metastatic activity to target organs. Analysis of clinical samples showed a robust association between high EPCR levels and poor prognosis, particularly in stage I patients.
conclusionsEPCR and its ligand APC promote cell survival that contributes to tumor cell endurance to stress favoring prometastatic activity of lung adenocarcinoma. EPCR/APC is a novel target of relevance in the clinical outcome of early-stage lung cancer.
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