Protease-activated receptors, apoptosis and tumor growth.
Protease-activated receptors (PARs) are G-protein-coupled receptors (GPCRs) that are activated by a unique proteolytic mechanism. Besides the important role of blood coagulation factors in preventing bleeding after vascular injury, these serine proteinases actively engage target cells thereby fulfilling critical functions in cell biology. Cellular responses triggered by coagulation factor-induced PAR activation suggest that PARs play an important role in proliferation, survival and/or malignant transformation of tumor cells. Indeed, PAR expression correlates with cancer malignancy and clinical studies show that anticoagulant treatment is beneficial in cancer patients. In this review, we provide an overview on the PAR family, their mode of activation and mechanisms by which PAR signaling is terminated. In addition, we discuss the relationship between blood coagulation and cancer biology focusing on the potential role of PAR-induced modulation of cell survival, apoptosis and tumor growth.
Borensztajn
Keren S
KS
Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands. K.S.Borensztajn@amc.uva.nl
Spek
C Arnold
CA
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001779:Blood Coagulation Factors / Q000502:physiology*; D020169:Caspases / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D017124:Conserved Sequence; D004789:Enzyme Activation; D020962:Heterotrimeric GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009369:Neoplasms / Q000097:blood / Q000473:pathology*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D044462:Receptors, Proteinase-Activated / Q000819:agonists / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D012243:Rhodopsin / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D019851:Thrombophilia / Q000209:etiology / Q000503:physiopathology; D013925:Thromboplastin / Q000502:physiology
D001779:Blood Coagulation Factors; D009363:Neoplasm Proteins; D044462:Receptors, Proteinase-Activated; D012243:Rhodopsin; D013925:Thromboplastin; D020169:Caspases; D020962:Heterotrimeric GTP-Binding Proteins