ArticleJournal of hematology & oncology2017
EPCR promotes breast cancer progression by altering SPOCK1/testican 1-mediated 3D growth.
Article in Journal of hematology & oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Testican-1 activates Wnt/β-Catenin signaling to drive colorectal cancer progression.Oncogenesis · 2026Article
- SPOCK1 acts as a negative regulator of ferroptosis in non-small cell lung cancer.NPJ precision oncology · 2026Article
- Proteoglycans in Breast Cancer: Friends and Foes.Biomolecules · 2025Review
- SPOCK: Master regulator of malignant tumors (Review).Molecular medicine reports · 2024Review
- Stromal cells in the tumor microenvironment: accomplices of tumor progression?Cell death & disease · 2023Review
- New insights into vitamin K biology with relevance to cancer.Trends in molecular medicine · 2022Review
- Multiomic analysis of the function ofThe Journal of international medical research · 2021Article
- Article
- SPOCK1: a multi-domain proteoglycan at the crossroads of extracellular matrix remodeling and cancer development.American journal of cancer research · 2020Review
- SPOCK1 Involvement in Epithelial-to-Mesenchymal Transition: A New Target in Cancer Therapy?Cancer management and research · 2020Review
- Proteoglycans as Mediators of Cancer Tissue Mechanics.Frontiers in cell and developmental biology · 2020Review
- Will donor-derived neoplasia be problematic after clinical pig organ or cell xenotransplantation?Xenotransplantation · 2019Review
- Review
- NR2C2-uORF targeting UCA1-miR-627-5p-NR2C2 feedback loop to regulate the malignant behaviors of glioma cells.Cell death & disease · 2018Article
- Mutual concessions and compromises between stromal cells and cancer cells: driving tumor development and drug resistance.Cellular oncology (Dordrecht, Netherlands) · 2018Review
- EPCR promotes MGC803 human gastric cancer cell tumor angiogenesisOncology letters · 2018Article
- Endothelial cell protein C receptor-dependent signaling.Current opinion in hematology · 2018Review
- Recent advances of highly selective CDK4/6 inhibitors in breast cancer.Journal of hematology & oncology · 2017Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundActivated protein C/endothelial protein C receptor (APC/EPCR) axis is physiologically involved in anticoagulant and cytoprotective activities in endothelial cells. Emerging evidence indicates that EPCR also plays a role in breast stemness and human tumorigenesis. Yet, its contribution to breast cancer progression and metastasis has not been elucidated.
methodsTranscriptomic status of EPCR was examined in a cohort of 286 breast cancer patients. Cell growth kinetics was evaluated in control and EPCR and SPARC/osteonectin, Cwcv, and kazal-like domains proteoglycan (SPOCK1/testican 1) silenced breast cancer cells in 2D, 3D, and in co-culture conditions. Orthotopic tumor growth and lung and osseous metastases were evaluated in several human and murine xenograft breast cancer models. Tumor-stroma interactions were further studied in vivo by immunohistochemistry and flow cytometry. An EPCR-induced gene signature was identified by microarray analysis.
resultsAnalysis of a cohort of breast cancer patients revealed an association of high EPCR levels with adverse clinical outcome. Interestingly, EPCR knockdown did not affect cell growth kinetics in 2D but significantly reduced cell growth in 3D cultures. Using several human and murine xenograft breast cancer models, we showed that EPCR silencing reduced primary tumor growth and secondary outgrowths at metastatic sites, including the skeleton and the lungs. Interestingly, these effects were independent of APC ligand stimulation in vitro and in vivo. Transcriptomic analysis of EPCR-silenced tumors unveiled an effect mediated by matricellular secreted proteoglycan SPOCK1/testican 1. Interestingly, SPOCK1 silencing suppressed in vitro 3D growth. Moreover, SPOCK1 ablation severely decreased orthotopic tumor growth and reduced bone metastatic osteolytic tumors. High SPOCK1 levels were also associated with poor clinical outcome in a subset breast cancer patients. Our results suggest that EPCR through SPOCK1 confers a cell growth advantage in 3D promoting breast tumorigenesis and metastasis.
conclusionsEPCR represents a clinically relevant factor associated with poor outcome and a novel vulnerability to develop combination therapies for breast cancer patients.
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