[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-383672-105":59,"doc-detail-383672-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","tumor-expressed-factor-vii-is-associated-with-survival-and-regulates-tumor-progression-in-breast-cancer","Tumor-expressed factor VII is associated with survival and regulates tumor progression in breast cancer","","Breast cancer progression is linked to a procoagulant microenvironment, where tissue factor (TF) and factor VII (FVII) participate in coagulation and signaling. This study shows that increased, tumor-expressed FVII levels in breast cancer specimens correlate with tumor progression and liver metastasis. In breast cancer models, tumor FVII drives epithelial-to-mesenchymal transition (EMT)-like changes, invasion, and prometastatic gene expression while promoting tumor growth in vivo. In contrast, liver-derived FVII can counter metastasis effects, and results clarify roles of endothelial protein C receptor and the canonical TF:PAR2 pathway.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/tumor-expressed-factor-vii-is-associated-with-survival-and-regulates-tumor-progression-in-breast-cancer/383672/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/tumor-expressed-factor-vii-is-associated-with-survival-and-regulates-tumor-progression-in-breast-cancer/383672.png","ImageObject",300,407,{"name":92,"@type":93},"Aurelia","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How does tumor-expressed FVII influence breast cancer progression?","Question",{"text":112,"@type":113},"Tumor-expressed factor VII promotes EMT-like changes, cancer cell invasion, and prometastatic gene expression, leading to increased tumor growth and liver metastasis in vivo.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What role does the TF:PAR2 pathway play in FVII-driven effects?",{"text":117,"@type":113},"The canonical TF:PAR2 pathway mediates signaling; recombinant activated FVII acting via this pathway inhibits prometastatic gene expression, counter to tumor-expressed FVII effects.",{"name":119,"@type":110,"acceptedAnswer":120},"How do tumor-expressed and liver-derived FVII differ in their impact on metastasis?",{"text":121,"@type":113},"Tumor-expressed FVII promotes EMT and metastasis, whereas liver-derived FVII was observed to inhibit metastasis, indicating opposing effects on EMT and metastatic progression.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},383672,1791288782,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},1099514068365,"https://ap-avatar.wpscdn.com/avatar/10000253d8d9f28188e?_k=1776742907772140068","REGULAR ARTICLE  \nTumor-expressed factor VII is associated with survival and regulates tumor progression in breast cancer  \nChantal Kroone, 1, * Chris Tieken, 1, * Begüm Kocatürk, 1, * Madelon Paauwe, 1 Erik J. Blok,2 Betül Ünlü, 1 Yascha W. van den Berg, 1 Eliana Stanganello, 1 Maaike Y. Kapteijn, 1 Nathalie Swier, 1 Xi Zhang,2 Danique E. M. Duits, 1 Yazhi Lin, 1 Lisa V. E. Oostenbrink, 1 Rob F. P. van den Akker, 1 Laurent O. Mosnier,3 Lukas J. Hawinkels,4 Bart J. M. van Vlijmen, 1 Wolfram Ruf,5, 6 Peter J. Kuppen,2 Suzanne C. Cannegieter,7 Jeroen T. Buijs, 1 and Henri H. Versteeg 1  \n1 Department of Internal Medicine, Einthoven Laboratory for Experimental Vascular Medicine, and 2 Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands; 3 Department of Molecular Medicine, Scripps Research, La Jolla, CA; 4 Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands; 5 Department of Immunology and Microbiology, Scripps Research, La Jolla, CA; 6 Center for Thrombosis and Hemostasis, Johannes Gutenberg University Medical Center, Mainz, Germany; and 7 Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands  \nKey Points  \n• Breast tumor– produced coagulation FVII induces EMT and liver metastasis via endothelial protein C receptor.  \n• Blood-borne FVII antagonizes the effects of tumor-expressed FVII by activating the TF-PAR2 axis.  \nCancer enhances the risk of venous thromboembolism, but a hypercoagulant microenvironment also promotes cancer progression. Although anticoagulants have been suggested as a potential anticancer treatment, clinical studies on the effect of such modalities on cancer progression have not yet been successful for unknown reasons. In normal physiology, complex formation between the subendothelial-expressed tissue factor (TF) and the blood-borne liver-derived factor VII (FVII) results in induction of the extrinsic coagulation cascade and intracellular signaling via protease-activated receptors (PARs) . In cancer, TF is overexpressed and linked to poor prognosis. Here, we report that increased levels of FVII are also observed in breast cancer specimens and are associated with tumor progression and metastasis to the liver. In breast cancer cell lines, tumor-expressed FVII drives changes reminiscent of epithelial-to-mesenchymal transition (EMT), tumor cell invasion, and expression of the prometastatic genes, SNAI2 and SOX9 . In vivo, tumorexpressed FVII enhanced tumor growth and liver metastasis. Surprisingly, liver-derived FVII appeared to inhibit metastasis. Finally, tumor-expressed FVII-induced prometastatic gene expression independent ofTF but required a functional endothelial protein C receptor, whereas recombinant activated FVII acting via the canonical TF:PAR2 pathway inhibited prometastatic gene expression. Here, we propose that tumor-expressed FVII and liverderived FVII have opposing effects on EMT and metastasis.  \nIntroduction  \nIncreasing evidence points toward a role for a procoagulant microenvironment in cancer progression.1 Coagulation factors such as factor VII (FVII) and FX, produced by the liver and present in the circulation, are part of this tumor milieu and can bind the initiator of coagulation tissue factor (TF) . TF is broadly  \nSubmitted 29 June 2022; accepted 28 February 2023; prepublished online on Blood Advances First Edition 15 March 2023. [https://doi.org/10.1182/](https://doi.org/10.1182/)[ ](https://doi.org/10.1182/)[bloodadvances.2022008455](bloodadvances.2022008455.)[.](bloodadvances.2022008455.)  \n*C.K., C.T., and B.K. contributed equally to this study.  \nMicroarray data reported in this article have been deposited in the Gene Expression Omnibus database (accession number GSE120047) .  \nAvailability of human tumors is restricted owing to ethical considerations. Cell lines and antibodies are freely available. Data are available on request from the corresponding author, Henri","cbCaiqiXEMl6uRqN","https://ap.wps.com/l/cbCaiqiXEMl6uRqN","pdf",2170029,13,"English","# Key Points\n# Introduction\n# Methods\n## Patient material","[{\"question\":\"How does tumor-expressed FVII influence breast cancer progression?\",\"answer\":\"Tumor-expressed factor VII promotes EMT-like changes, cancer cell invasion, and prometastatic gene expression, leading to increased tumor growth and liver metastasis in vivo.\"},{\"question\":\"What role does the TF:PAR2 pathway play in FVII-driven effects?\",\"answer\":\"The canonical TF:PAR2 pathway mediates signaling; recombinant activated FVII acting via this pathway inhibits prometastatic gene expression, counter to tumor-expressed FVII effects.\"},{\"question\":\"How do tumor-expressed and liver-derived FVII differ in their impact on metastasis?\",\"answer\":\"Tumor-expressed FVII promotes EMT and metastasis, whereas liver-derived FVII was observed to inhibit metastasis, indicating opposing effects on EMT and metastatic progression.\"}]","Tumor-expressed factor VII is associated with survival and regulates tumor progression in breast cancer | PDF",1790258692,33]