title: Protease-activated receptors - biology and role in cancer.
abstract: The fact that blood coagulation disorders may accompany malignant disease is well established. However, many studies have shown that components of the haemostatic system may also elicit signaling leading to cancer developement and progression. The potential mechanism by which coagulation factors play a role in cancer invasion is not completely understood, but one hypothesis is that protease-activated receptors (PARs) play a prominent role. PARs are transmembrane G-protein-coupled receptors (GPCRs) that are activated by a unique proteolytic mechanism. They have important functions in haemostasis and inflammation but may also be implicated in cancer cell progression. Thrombin, tissue factor (TF) and matrix metalloproteinases (MMPs) are the main activators of these receptors. The mechanism of persistent activation of PARs was also described in cancer cells. Here, we discuss the physiological and pathological role of PARs with a particular focus on PARs' contribution to cancer biology. We also present therapeutic options tailored specifically to inhibition of PAR-induced signalling in cancer patients.
authors.affiliation: Klinika Onkologii Uniwersytetu Medycznego w Białymstoku; Białostockie Centrum Onkologii.
authors.forename: Dominika
authors.initials: D
authors.lastname: Hempel
authors.affiliation: Klinika Onkologii Uniwersytetu Medycznego w Białymstoku; Białostockie Centrum Onkologii.
authors.forename: Ewa
authors.initials: E
authors.lastname: Sierko
authors.affiliation: Klinika Onkologii Uniwersytetu Medycznego w Białymstoku; Białostockie Centrum Onkologii.
authors.forename: Marek Z
authors.initials: MZ
authors.lastname: Wojtukiewicz
mesh_terms: D001779:Blood Coagulation Factors / Q000378:metabolism; D006487:Hemostasis / Q000187:drug effects*; D006490:Hemostatics; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009369:Neoplasms / Q000473:pathology*; D059748:Proteolysis / Q000187:drug effects; D044462:Receptors, Proteinase-Activated / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013917:Thrombin / Q000378:metabolism
chemical_list: D001779:Blood Coagulation Factors; D006490:Hemostatics; D044462:Receptors, Proteinase-Activated; D013917:Thrombin