title: Protease-activated receptors (PARs)--biology and role in cancer invasion and metastasis.
abstract: Although many studies have demonstrated that components of the hemostatic system may be involved in signaling leading to cancer progression, the potential mechanisms by which they contribute to cancer dissemination are not yet precisely understood. Among known coagulant factors, tissue factor (TF) and thrombin play a pivotal role in cancer invasion. They may be generated in the tumor microenvironment independently of blood coagulation and can induce cell signaling through activation of protease-activated receptors (PARs). PARs are transmembrane G-protein-coupled receptors (GPCRs) that are activated by a unique proteolytic mechanism. They play important roles in vascular physiology, neural tube closure, hemostasis, and inflammation. All of these agents (TF, thrombin, PARs-mainly PAR-1 and PAR-2) are thought to promote cancer invasion and metastasis at least in part by facilitating tumor cell migration, angiogenesis, and interactions with host vascular cells, including platelets, fibroblasts, and endothelial cells lining blood vessels. Here, we discuss the role of PARs and their activators in cancer progression, focusing on TF- and thrombin-mediated actions. Therapeutic options tailored specifically to inhibit PAR-induced signaling in cancer patients are presented as well.
authors.affiliation: Department of Oncology, Medical University of Bialystok, 12 Ogrodowa St., 15-025, Bialystok, Poland. mzwojtukiewicz@gmail.com.|Department of Clinical Oncology, Comprehensive Cancer Center , Bialystok, Poland. mzwojtukiewicz@gmail.com.
authors.forename: Marek Z
authors.initials: MZ
authors.lastname: Wojtukiewicz
authors.affiliation: Department of Oncology, Medical University of Bialystok, 12 Ogrodowa St., 15-025, Bialystok, Poland.|Department of Clinical Oncology, Comprehensive Cancer Center , Bialystok, Poland.|Department of Radiotherapy, Comprehensive Cancer Center, Bialystok, Poland.
authors.forename: Dominika
authors.initials: D
authors.lastname: Hempel
authors.affiliation: Department of Oncology, Medical University of Bialystok, 12 Ogrodowa St., 15-025, Bialystok, Poland.|Department of Clinical Oncology, Comprehensive Cancer Center , Bialystok, Poland.|Department of Radiotherapy, Comprehensive Cancer Center, Bialystok, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Sierko
authors.affiliation: Bioactive Lipids Research Program, Department of Pathology-School of Medicine, Detroit, MI, USA.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Tucker
authors.affiliation: Bioactive Lipids Research Program, Department of Pathology-School of Medicine, Detroit, MI, USA.|Department of Chemistry, Wayne State University, Detroit, MI, USA.|Department of Oncology, Karmanos Cancer Institute, Detroit, MI, USA.
authors.forename: Kenneth V
authors.initials: KV
authors.lastname: Honn
mesh_terms: D001792:Blood Platelets / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000473:pathology*; D009369:Neoplasms / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology; D044463:Receptor, PAR-1 / Q000378:metabolism*; D044464:Receptor, PAR-2 / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D059016:Tumor Microenvironment / Q000502:physiology
chemical_list: D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D013925:Thromboplastin; D013917:Thrombin
keywords: Cancer invasion; Metastasis; Microenvironment; PAR-1; PAR-2; Thrombin; Tissue factor