Download PDF
Semin Thromb Hemost 2015; 41(07): 691-699
DOI: 10.1055/s-0035-1564046
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Tissue Factor Noncoagulant Signaling: Mechanisms and Implications for Cell Migration and Apoptosis

Mikael Åberg
1   Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden
,
Oskar Eriksson
1   Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden
,
Agneta Siegbahn
1   Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden
› Author Affiliations
Further Information

Publication History

Publication Date:
29 September 2015 (online)

    Permissions and Reprints

Abstract

Tissue factor (TF) is a 47-kDa transmembrane glycoprotein and the main initiator of the blood coagulation cascade. Binding to its ligand factor VIIa (FVIIa) also initiates noncoagulant signaling with broad biological implications. In this review, we discuss how TF interacts with other cell-surface proteins, which affect biological functions such as cell migration and cell survival. A vast number of publications have demonstrated the importance of TF-induced activation of protease-activated receptors, but recently published research has indicated a more complicated picture. As it has been discovered that TF interacts with integrins and receptor tyrosine kinases, novel signaling mechanisms for the TF/FVIIa complex have been presented. The knowledge of these new aspects of TF signaling may, for instance, facilitate the development of new treatment strategies for cancer and acute coronary syndromes, two examples of diseases characterized by aberrant TF expression and signaling.

Keywords

tissue factor - factor VIIa - intracellular signaling - cell migration - apoptosis
 

  • References

  • 1 Lawson JH, Butenas S, Mann KG. The evaluation of complex-dependent alterations in human factor VIIa. J Biol Chem 1992; 267 (7) 4834-4843
    PubMedGoogle Scholar
  • 2 Hoffman M, Monroe III DM. A cell-based model of hemostasis. Thromb Haemost 2001; 85 (6) 958-965
    PubMedGoogle Scholar
  • 3 Chen VM, Hogg PJ. Encryption and decryption of tissue factor. J Thromb Haemost 2013; 11 (Suppl. 01) 277-284
    CrossrefPubMedGoogle Scholar
  • 4 Drake TA, Morrissey JH, Edgington TS. Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis. Am J Pathol 1989; 134 (5) 1087-1097
    PubMedGoogle Scholar
  • 5 Fleck RA, Rao LV, Rapaport SI, Varki N. Localization of human tissue factor antigen by immunostaining with monospecific, polyclonal anti-human tissue factor antibody. Thromb Res 1990; 59 (2) 421-437
    CrossrefPubMedGoogle Scholar
  • 6 Donati MB, Lorenzet R. Thrombosis and cancer: 40 years of research. Thromb Res 2012; 129 (3) 348-352
    Google Scholar
  • 7 Steffel J, Lüscher TF, Tanner FC. Tissue factor in cardiovascular diseases: molecular mechanisms and clinical implications. Circulation 2006; 113 (5) 722-731
    CrossrefPubMedGoogle Scholar
  • 8 Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010; 140 (6) 883-899
    CrossrefPubMedGoogle Scholar
  • 9 Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005; 352 (16) 1685-1695
    CrossrefPubMedGoogle Scholar
  • 10 Osterud B. Cellular interactions in tissue factor expression by blood monocytes. Blood Coagul Fibrinolysis 1995; 6 (Suppl. 01) S20-S25
    PubMedGoogle Scholar
  • 11 Ernofsson M, Siegbahn A. Platelet-derived growth factor-BB and monocyte chemotactic protein-1 induce human peripheral blood monocytes to express tissue factor. Thromb Res 1996; 83 (4) 307-320
    CrossrefPubMedGoogle Scholar
  • 12 Rong Y, Post DE, Pieper RO, Durden DL, Van Meir EG, Brat DJ. PTEN and hypoxia regulate tissue factor expression and plasma coagulation by glioblastoma. Cancer Res 2005; 65 (4) 1406-1413
    CrossrefPubMedGoogle Scholar
  • 13 Yu JL, May L, Lhotak V , et al. Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumor progression and angiogenesis. Blood 2005; 105 (4) 1734-1741
    CrossrefPubMedGoogle Scholar
  • 14 Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost 2007; 5 (3) 632-634
    CrossrefPubMedGoogle Scholar
  • 15 Ahamed J, Versteeg HH, Kerver M , et al. Disulfide isomerization switches tissue factor from coagulation to cell signaling. Proc Natl Acad Sci U S A 2006; 103 (38) 13932-13937
    CrossrefPubMedGoogle Scholar
  • 16 Bogdanov VY, Balasubramanian V, Hathcock J, Vele O, Lieb M, Nemerson Y. Alternatively spliced human tissue factor: a circulating, soluble, thrombogenic protein. Nat Med 2003; 9 (4) 458-462
    Google Scholar
  • 17 Kocatürk B, Van den Berg YW, Tieken C , et al. Alternatively spliced tissue factor promotes breast cancer growth in a β1 integrin-dependent manner. Proc Natl Acad Sci U S A 2013; 110 (28) 11517-11522
    CrossrefPubMedGoogle Scholar
  • 18 Srinivasan R, Bogdanov VY. Splice variants of Tissue Factor and integrin-mediated signaling. Thromb Res 2012; 129 (Suppl. 02) S34-S37
    CrossrefPubMedGoogle Scholar
  • 19 Åberg M, Siegbahn A. Tissue factor non-coagulant signaling - molecular mechanisms and biological consequences with a focus on cell migration and apoptosis. J Thromb Haemost 2013; 11 (5) 817-825
    CrossrefPubMedGoogle Scholar
  • 20 Siegbahn A, Johnell M, Rorsman C, Ezban M, Heldin CH, Rönnstrand L. Binding of factor VIIa to tissue factor on human fibroblasts leads to activation of phospholipase C and enhanced PDGF-BB-stimulated chemotaxis. Blood 2000; 96 (10) 3452-3458
    PubMedGoogle Scholar
  • 21 Sutherland MR, Ruf W, Pryzdial EL. Tissue factor and glycoprotein C on herpes simplex virus type 1 are protease-activated receptor 2 cofactors that enhance infection. Blood 2012; 119 (15) 3638-3645
    CrossrefPubMedGoogle Scholar
  • 22 Siegbahn A, Johnell M, Sorensen BB, Petersen LC, Heldin CH. Regulation of chemotaxis by the cytoplasmic domain of tissue factor. Thromb Haemost 2005; 93 (1) 27-34
    PubMedGoogle Scholar
  • 23 Mueller BM, Reisfeld RA, Edgington TS, Ruf W. Expression of tissue factor by melanoma cells promotes efficient hematogenous metastasis. Proc Natl Acad Sci U S A 1992; 89 (24) 11832-11836
    CrossrefPubMedGoogle Scholar
  • 24 Røttingen JA, Enden T, Camerer E, Iversen JG, Prydz H. Binding of human factor VIIa to tissue factor induces cytosolic Ca2+ signals in J82 cells, transfected COS-1 cells, Madin-Darby canine kidney cells and in human endothelial cells induced to synthesize tissue factor. J Biol Chem 1995; 270 (9) 4650-4660
    CrossrefPubMedGoogle Scholar
  • 25 Spicer EK, Horton R, Bloem L , et al. Isolation of cDNA clones coding for human tissue factor: primary structure of the protein and cDNA. Proc Natl Acad Sci U S A 1987; 84 (15) 5148-5152
    CrossrefPubMedGoogle Scholar
  • 26 Morrissey JH, Fakhrai H, Edgington TS. Molecular cloning of the cDNA for tissue factor, the cellular receptor for the initiation of the coagulation protease cascade. Cell 1987; 50 (1) 129-135
    CrossrefPubMedGoogle Scholar
  • 27 Carson SD, Bromberg ME. Tissue factor encryption/de-encryption is not altered in the absence of the cytoplasmic domain. Thromb Haemost 2000; 84 (4) 657-663
    PubMedGoogle Scholar
  • 28 Camerer E, Rottingen JA, Iversen JG, Prydz H. Coagulation factors VII and X induce Ca2+ oscillations in Madin-Darby canine kidney cells only when proteolytically active. J Biol Chem 1996; 271 (46) 29034-29042
    CrossrefPubMedGoogle Scholar
  • 29 Sørensen BB, Freskgård PO, Nielsen LS, Rao LV, Ezban M, Petersen LC. Factor VIIa-induced p44/42 mitogen-activated protein kinase activation requires the proteolytic activity of factor VIIa and is independent of the tissue factor cytoplasmic domain. J Biol Chem 1999; 274 (30) 21349-21354
    CrossrefPubMedGoogle Scholar
  • 30 Franchini M, Mannucci PM. Thrombin and cancer: from molecular basis to therapeutic implications. Semin Thromb Hemost 2012; 38 (1) 95-101
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Vu TK, Hung DT, Wheaton VI, Coughlin SR. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 1991; 64 (6) 1057-1068
    CrossrefPubMedGoogle Scholar
  • 32 Nystedt S, Emilsson K, Wahlestedt C, Sundelin J. Molecular cloning of a potential proteinase activated receptor. Proc Natl Acad Sci U S A 1994; 91 (20) 9208-9212
    CrossrefPubMedGoogle Scholar
  • 33 Nystedt S, Emilsson K, Larsson AK, Strömbeck B, Sundelin J. Molecular cloning and functional expression of the gene encoding the human proteinase-activated receptor 2. Eur J Biochem 1995; 232 (1) 84-89
    CrossrefPubMedGoogle Scholar
  • 34 Molino M, Woolkalis MJ, Reavey-Cantwell J , et al. Endothelial cell thrombin receptors and PAR-2. Two protease-activated receptors located in a single cellular environment. J Biol Chem 1997; 272 (17) 11133-11141
    CrossrefPubMedGoogle Scholar
  • 35 Camerer E, Huang W, Coughlin SR. Tissue factor- and factor X-dependent activation of protease-activated receptor 2 by factor VIIa. Proc Natl Acad Sci U S A 2000; 97 (10) 5255-5260
    CrossrefPubMedGoogle Scholar
  • 36 Riewald M, Ruf W. Mechanistic coupling of protease signaling and initiation of coagulation by tissue factor. Proc Natl Acad Sci U S A 2001; 98 (14) 7742-7747
    CrossrefPubMedGoogle Scholar
  • 37 Hjortoe GM, Petersen LC, Albrektsen T , et al. Tissue factor-factor VIIa-specific up-regulation of IL-8 expression in MDA-MB-231 cells is mediated by PAR-2 and results in increased cell migration. Blood 2004; 103 (8) 3029-3037
    Google Scholar
  • 38 Colognato R, Slupsky JR, Jendrach M, Burysek L, Syrovets T, Simmet T. Differential expression and regulation of protease-activated receptors in human peripheral monocytes and monocyte-derived antigen-presenting cells. Blood 2003; 102 (7) 2645-2652
    CrossrefPubMedGoogle Scholar
  • 39 Toschi V, Gallo R, Lettino M , et al. Tissue factor modulates the thrombogenicity of human atherosclerotic plaques. Circulation 1997; 95 (3) 594-599
    CrossrefPubMedGoogle Scholar
  • 40 Disse J, Petersen HH, Larsen KS , et al. The endothelial protein C receptor supports tissue factor ternary coagulation initiation complex signaling through protease-activated receptors. J Biol Chem 2011; 286 (7) 5756-5767
    CrossrefPubMedGoogle Scholar
  • 41 Zioncheck TF, Roy S, Vehar GA. The cytoplasmic domain of tissue factor is phosphorylated by a protein kinase C-dependent mechanism. J Biol Chem 1992; 267 (6) 3561-3564
    PubMedGoogle Scholar
  • 42 Dorfleutner A, Ruf W. Regulation of tissue factor cytoplasmic domain phosphorylation by palmitoylation. Blood 2003; 102 (12) 3998-4005
    CrossrefPubMedGoogle Scholar
  • 43 Ahamed J, Ruf W. Protease-activated receptor 2-dependent phosphorylation of the tissue factor cytoplasmic domain. J Biol Chem 2004; 279 (22) 23038-23044
    Google Scholar
  • 44 Ettelaie C, Elkeeb AM, Maraveyas A, Collier ME. p38α phosphorylates serine 258 within the cytoplasmic domain of tissue factor and prevents its incorporation into cell-derived microparticles. Biochim Biophys Acta 2013; 1833 (3) 613-621
    CrossrefPubMedGoogle Scholar
  • 45 Ott I, Fischer EG, Miyagi Y, Mueller BM, Ruf W. A role for tissue factor in cell adhesion and migration mediated by interaction with actin-binding protein 280. J Cell Biol 1998; 140 (5) 1241-1253
    Google Scholar
  • 46 Collier ME, Maraveyas A, Ettelaie C. Filamin-A is required for the incorporation of tissue factor into cell-derived microvesicles. Thromb Haemost 2014; 111 (4) 647-655
    PubMedGoogle Scholar
  • 47 Dorfleutner A, Hintermann E, Tarui T, Takada Y, Ruf W. Cross-talk of integrin alpha3beta1 and tissue factor in cell migration. Mol Biol Cell 2004; 15 (10) 4416-4425
    CrossrefPubMedGoogle Scholar
  • 48 Versteeg HH, Schaffner F, Kerver M , et al. Inhibition of tissue factor signaling suppresses tumor growth. Blood 2008; 111 (1) 190-199
    CrossrefPubMedGoogle Scholar
  • 49 Lane DA, Philippou H, Huntington JA. Directing thrombin. Blood 2005; 106 (8) 2605-2612
    CrossrefPubMedGoogle Scholar
  • 50 Debela M, Beaufort N, Magdolen V , et al. Structures and specificity of the human kallikrein-related peptidases KLK 4, 5, 6, and 7. Biol Chem 2008; 389 (6) 623-632
    PubMedGoogle Scholar
  • 51 Eriksson O, Ramström M, Hörnaeus K, Bergquist J, Mokhtari D, Siegbahn A. The Eph tyrosine kinase receptors EphB2 and EphA2 are novel proteolytic substrates of tissue factor/coagulation factor VIIa. J Biol Chem 2014; 289 (47) 32379-32391
    CrossrefPubMedGoogle Scholar
  • 52 Janes PW, Nievergall E, Lackmann M. Concepts and consequences of Eph receptor clustering. Semin Cell Dev Biol 2012; 23 (1) 43-50
    CrossrefPubMedGoogle Scholar
  • 53 Braun J, Hoffmann SC, Feldner A , et al. Endothelial cell ephrinB2-dependent activation of monocytes in arteriosclerosis. Arterioscler Thromb Vasc Biol 2011; 31 (2) 297-305
    CrossrefPubMedGoogle Scholar
  • 54 Liu H, Devraj K, Möller K, Liebner S, Hecker M, Korff T. EphrinB-mediated reverse signalling controls junctional integrity and pro-inflammatory differentiation of endothelial cells. Thromb Haemost 2014; 112 (1) 151-163
    Article in Thieme ConnectPubMedGoogle Scholar
  • 55 Sakamoto A, Ishibashi-Ueda H, Sugamoto Y , et al. Expression and function of ephrin-B1 and its cognate receptor EphB2 in human atherosclerosis: from an aspect of chemotaxis. Clin Sci (Lond) 2008; 114 (10) 643-650
    CrossrefPubMedGoogle Scholar
  • 56 Butera D, Cook KM, Chiu J, Wong JW, Hogg PJ. Control of blood proteins by functional disulfide bonds. Blood 2014; 123 (13) 2000-2007
    CrossrefPubMedGoogle Scholar
  • 57 Metcalfe C, Cresswell P, Ciaccia L, Thomas B, Barclay AN. Labile disulfide bonds are common at the leucocyte cell surface. Open Biol 2011; 1 (3) 110010
    CrossrefPubMedGoogle Scholar
  • 58 Heldin CH. Targeting the PDGF signaling pathway in tumor treatment. Cell Commun Signal 2013; 11: 97
    CrossrefPubMedGoogle Scholar
  • 59 Rubin K, Tingström A, Hansson GK , et al. Induction of B-type receptors for platelet-derived growth factor in vascular inflammation: possible implications for development of vascular proliferative lesions. Lancet 1988; 1 (8599) 1353-1356
    PubMedGoogle Scholar
  • 60 Sano H, Sudo T, Yokode M , et al. Functional blockade of platelet-derived growth factor receptor-beta but not of receptor-alpha prevents vascular smooth muscle cell accumulation in fibrous cap lesions in apolipoprotein E-deficient mice. Circulation 2001; 103 (24) 2955-2960
    CrossrefPubMedGoogle Scholar
  • 61 Panda AC, Grammatikakis I, Yoon JH, Abdelmohsen K. Posttranscriptional regulation of insulin family ligands and receptors. Int J Mol Sci 2013; 14 (9) 19202-19229
    CrossrefPubMedGoogle Scholar
  • 62 Wiiger MT, Prydz H. The epidermal growth factor receptor (EGFR) and proline rich tyrosine kinase 2 (PYK2) are involved in tissue factor dependent factor VIIa signalling in HaCaT cells. Thromb Haemost 2004; 92 (1) 13-22
    PubMedGoogle Scholar
  • 63 Siegbahn A, Johnell M, Nordin A, Aberg M, Velling T. TF/FVIIa transactivate PDGFRbeta to regulate PDGF-BB-induced chemotaxis in different cell types: involvement of Src and PLC. Arterioscler Thromb Vasc Biol 2008; 28 (1) 135-141
    PubMedGoogle Scholar
  • 64 Åberg M, Eriksson O, Mokhtari D, Siegbahn A. Tissue factor/factor VIIa induces cell survival and gene transcription by transactivation of the insulin-like growth factor 1 receptor. Thromb Haemost 2014; 111 (4) 748-760
    PubMedGoogle Scholar
  • 65 Daub H, Weiss FU, Wallasch C, Ullrich A. Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors. Nature 1996; 379 (6565) 557-560
    CrossrefPubMedGoogle Scholar
  • 66 Prenzel N, Zwick E, Daub H , et al. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. Nature 1999; 402 (6764) 884-888
    PubMedGoogle Scholar
  • 67 Song S, Rosen KM, Corfas G. Biological function of nuclear receptor tyrosine kinase action. Cold Spring Harb Perspect Biol 2013; 5 (7) 5
    PubMedGoogle Scholar
  • 68 Lin SY, Makino K, Xia W , et al. Nuclear localization of EGF receptor and its potential new role as a transcription factor. Nat Cell Biol 2001; 3 (9) 802-808
    CrossrefPubMedGoogle Scholar
  • 69 Camerer E, Gjernes E, Wiiger M, Pringle S, Prydz H. Binding of factor VIIa to tissue factor on keratinocytes induces gene expression. J Biol Chem 2000; 275 (9) 6580-6585
    CrossrefPubMedGoogle Scholar
  • 70 Muth H, Kreis I, Zimmermann R, Tillmanns H, Hölschermann H. Differential gene expression in activated monocyte-derived macrophages following binding of factor VIIa to tissue factor. Thromb Haemost 2005; 94 (5) 1028-1034
    PubMedGoogle Scholar
  • 71 Albrektsen T, Sørensen BB, Hjortø GM, Fleckner J, Rao LV, Petersen LC. Transcriptional program induced by factor VIIa-tissue factor, PAR1 and PAR2 in MDA-MB-231 cells. J Thromb Haemost 2007; 5 (8) 1588-1597
    CrossrefPubMedGoogle Scholar
  • 72 Kask L, Jorsback A, Winkvist M , et al. Identification of novel downstream molecules of tissue factor activation by comparative proteomic analysis. J Proteome Res 2014; 13 (2) 477-488
    CrossrefPubMedGoogle Scholar
  • 73 Müller M, Albrecht S, Gölfert F , et al. Localization of tissue factor in actin-filament-rich membrane areas of epithelial cells. Exp Cell Res 1999; 248 (1) 136-147
    CrossrefPubMedGoogle Scholar
  • 74 Lauffenburger DA, Horwitz AF. Cell migration: a physically integrated molecular process. Cell 1996; 84 (3) 359-369
    CrossrefPubMedGoogle Scholar
  • 75 Hooshmand-Rad R, Claesson-Welsh L, Wennström S, Yokote K, Siegbahn A, Heldin CH. Involvement of phosphatidylinositide 3′-kinase and Rac in platelet-derived growth factor-induced actin reorganization and chemotaxis. Exp Cell Res 1997; 234 (2) 434-441
    CrossrefPubMedGoogle Scholar
  • 76 Ge L, Ly Y, Hollenberg M, DeFea K. A beta-arrestin-dependent scaffold is associated with prolonged MAPK activation in pseudopodia during protease-activated receptor-2-induced chemotaxis. J Biol Chem 2003; 278 (36) 34418-34426
    CrossrefPubMedGoogle Scholar
  • 77 Zoudilova M, Kumar P, Ge L, Wang P, Bokoch GM, DeFea KA. Beta-arrestin-dependent regulation of the cofilin pathway downstream of protease-activated receptor-2. J Biol Chem 2007; 282 (28) 20634-20646
    CrossrefPubMedGoogle Scholar
  • 78 Zhu T, Mancini JA, Sapieha P , et al. Cortactin activation by FVIIa/tissue factor and PAR2 promotes endothelial cell migration. Am J Physiol Regul Integr Comp Physiol 2011; 300 (3) R577-R585
    CrossrefPubMedGoogle Scholar
  • 79 Peña E, Arderiu G, Badimon L. Subcellular localization of tissue factor and human coronary artery smooth muscle cell migration. J Thromb Haemost 2012; 10 (11) 2373-2382
    CrossrefPubMedGoogle Scholar
  • 80 Peña E, Arderiu G, Badimon L. Tissue factor induces human coronary artery smooth muscle cell motility through Wnt-signalling. J Thromb Haemost 2013; 11 (10) 1880-1891
    PubMedGoogle Scholar
  • 81 Gessler F, Voss V, Dützmann S, Seifert V, Gerlach R, Kögel D. Inhibition of tissue factor/protease-activated receptor-2 signaling limits proliferation, migration and invasion of malignant glioma cells. Neuroscience 2010; 165 (4) 1312-1322
    CrossrefPubMedGoogle Scholar
  • 82 Guo D, Zhou H, Wu Y , et al. Involvement of ERK1/2/NF-κB signal transduction pathway in TF/FVIIa/PAR2-induced proliferation and migration of colon cancer cell SW620. Tumour Biol 2011; 32 (5) 921-930
    CrossrefPubMedGoogle Scholar
  • 83 Taniguchi T, Kakkar AK, Tuddenham EG, Williamson RC, Lemoine NR. Enhanced expression of urokinase receptor induced through the tissue factor-factor VIIa pathway in human pancreatic cancer. Cancer Res 1998; 58 (19) 4461-4467
    PubMedGoogle Scholar
  • 84 Siegbahn A. Cellular consequences upon factor VIIa binding to tissue factor. Haemostasis 2000; 30 (Suppl. 02) 41-47
    PubMedGoogle Scholar
  • 85 Sorensen BB, Rao LV, Tornehave D, Gammeltoft S, Petersen LC. Antiapoptotic effect of coagulation factor VIIa. Blood 2003; 102 (5) 1708-1715
    CrossrefPubMedGoogle Scholar
  • 86 Versteeg HH, Spek CA, Richel DJ, Peppelenbosch MP. Coagulation factors VIIa and Xa inhibit apoptosis and anoikis. Oncogene 2004; 23 (2) 410-417
    CrossrefPubMedGoogle Scholar
  • 87 Jiang X, Guo YL, Bromberg ME. Formation of tissue factor-factor VIIa-factor Xa complex prevents apoptosis in human breast cancer cells. Thromb Haemost 2006; 96 (2) 196-201
    PubMedGoogle Scholar
  • 88 Aberg M, Wickström M, Siegbahn A. Simvastatin induces apoptosis in human breast cancer cells in a NFkappaB-dependent manner and abolishes the anti-apoptotic signaling of TF/FVIIa and TF/FVIIa/FXa. Thromb Res 2008; 122 (2) 191-202
    CrossrefPubMedGoogle Scholar
  • 89 Pennarun B, Meijer A, de Vries EG, Kleibeuker JH, Kruyt F, de Jong S. Playing the DISC: turning on TRAIL death receptor-mediated apoptosis in cancer. Biochim Biophys Acta 2010; 1805 (2) 123-140
    PubMedGoogle Scholar
  • 90 Aberg M, Johnell M, Wickström M, Siegbahn A. Tissue Factor/FVIIa prevents the extrinsic pathway of apoptosis by regulation of the tumor suppressor Death-Associated Protein Kinase 1 (DAPK1). Thromb Res 2011; 127 (2) 141-148
    CrossrefPubMedGoogle Scholar
  • 91 Boltzen U, Eisenreich A, Antoniak S , et al. Alternatively spliced tissue factor and full-length tissue factor protect cardiomyocytes against TNF-α-induced apoptosis. J Mol Cell Cardiol 2012; 52 (5) 1056-1065
    CrossrefPubMedGoogle Scholar
  • 92 Carmeliet P, Mackman N, Moons L , et al. Role of tissue factor in embryonic blood vessel development. Nature 1996; 383 (6595) 73-75
    CrossrefPubMedGoogle Scholar