The Role of Tissue Factor In Signaling Pathways of Pathological
Conditions and Angiogenesis

Zahra      Heidari; Yasaman      Naeimzadeh; Jafar      Fallahi; Amir      Savardashtaki; Vahid      Razban; Sahar      Khajeh
doi:10.2174/0115665240258746230919165935
Abstract

Tissue factor (TF) is an integral transmembrane protein associated with the extrinsic coagulation pathway. TF gene expression is regulated in response to inflammatory cytokines, bacterial lipopolysaccharides, and mechanical injuries. TF activity may be affected by phosphorylation of its cytoplasmic domain and alternative splicing. TF acts as the primary initiator of physiological hemostasis, which prevents local bleeding at the injury site. However, aberrant expression of TF, accompanied by the severity of diseases and infections under various pathological conditions, triggers multiple signaling pathways that support thrombosis, angiogenesis, inflammation, and metastasis. Protease-activated receptors (PARs) are central in the downstream signaling pathways of TF. In this study, we have reviewed the TF signaling pathways in different pathological conditions, such as wound injury, asthma, cardiovascular diseases (CVDs), viral infections, cancer and pathological angiogenesis. Angiogenic activities of TF are critical in the repair of wound injuries and aggressive behavior of tumors, which are mainly performed by the actions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 (HIF1-α). Pro-inflammatory effects of TF have been reported in asthma, CVDs and viral infections, including COVID-19, which result in tissue hypertrophy, inflammation, and thrombosis. TF-FVII induces angiogenesis via clotting-dependent and -independent mechanisms. Clottingdependent angiogenesis is induced via the generation of thrombin and cross-linked fibrin network, which facilitate vessel infiltration and also act as a reservoir for endothelial cells (ECs) growth factors. Expression of TF in tumor cells and ECs triggers clotting-independent angiogenesis through induction of VEGF, urokinase-type plasminogen activator (uPAR), early growth response 1 (EGR1), IL8, and cysteine-rich angiogenic inducer 61 (Cyr61).
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[1]
Cañas CA, Cañas F, Bautista-Vargas M, Bonilla-Abadía F. Role of tissue factor in the pathogenesis of covid-19 and the possible ways to inhibit it. Clin Appl Thromb Hemost  2021; 27.
 [http://dx.doi.org/10.1177/10760296211003983] [PMID:  33784877]

[2]
Cimmino G, Cirillo P. Tissue factor: Newer concepts in thrombosis and its role beyond thrombosis and hemostasis. Cardiovasc Diagn Ther  2018; 8(5): 581-93.
 [http://dx.doi.org/10.21037/cdt.2018.10.14] [PMID:  30498683]

[3]
van den Berg YW, Osanto S, Reitsma PH, Versteeg HH. The relationship between tissue factor and cancer progression: Insights from bench and bedside. Blood  2012; 119(4): 924-32.
 [http://dx.doi.org/10.1182/blood-2011-06-317685] [PMID:  22065595]

[4]
Versteeg HH, Spek CA, Peppelenbosch MP, Richel DJ. Tissue factor and cancer metastasis: The role of intracellular and extracellular signaling pathways. Mol Med  2004; 10(1-6): 6-11.
 [http://dx.doi.org/10.2119/2003-00047.Versteeg] [PMID:  15502877]

[5]
Zarychta E, Ruszkowska-Ciastek B. Cooperation between angiogenesis, vasculogenesis, chemotaxis, and coagulation in breast cancer metastases development: Patho-physiological point of view. Biomedicines  2022; 10(2): 300.
 [http://dx.doi.org/10.3390/biomedicines10020300] [PMID:  35203510]

[6]
Censarek P, Bobbe A, Grandoch M, Schrör K, Weber AA. Alternatively spliced human tissue factor (asHTF) is not pro-coagulant. Thromb Haemost  2007; 97(1): 11-4.
 [http://dx.doi.org/10.1160/TH06-09-0524] [PMID:  17200764]

[7]
Bogdanov VY, Versteeg HH. Eds. Soluble tissue factor in the 21st century: Definitions, biochemistry, and pathophysiological role in thrombus formation Seminars in thrombosis and hemostasis. Semin Thromb Hemost  2015; 41(7): 700-7.

[8]
van den Berg YW, Versteeg HH. Alternatively spliced tissue factor. Hamostaseologie  2010; 30(3): 144-9.
 [http://dx.doi.org/10.1055/s-0037-1619043] [PMID:  20680231]

[9]
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): 458-62.
 [http://dx.doi.org/10.1038/nm841] [PMID:  12652293]

[10]
van den Berg YW, van den Hengel LG, Myers HR, et al. Alternatively spliced tissue factor induces angiogenesis through integrin ligation. Proc Natl Acad Sci   2009; 106(46): 19497-502.
 [http://dx.doi.org/10.1073/pnas.0905325106] [PMID:  19875693]

[11]
Signaevsky M, Hobbs J, Doll J, Liu N, Soff GA. Role of alternatively spliced tissue factor in pancreatic cancer growth and angiogenesis. Semin Thromb Hemost  2008; 34(2): 161-9.
 [http://dx.doi.org/10.1055/s-2008-1079256]

[12]
Giannarelli C, Alique M, Rodriguez DT, et al. Alternatively spliced tissue factor promotes plaque angiogenesis through the activation of hypoxia-inducible factor-1α and vascular endothelial growth factor signaling. Circulation  2014; 130(15): 1274-86.
 [http://dx.doi.org/10.1161/CIRCULATIONAHA.114.006614] [PMID:  25116956]

[13]
Chandradas S, Deikus G, Tardos JG, Bogdanov VY. Antagonistic roles of four SR proteins in the biosynthesis of alternatively spliced tissue factor transcripts in monocytic cells. J Leukoc Biol  2009; 87(1): 147-52.
 [http://dx.doi.org/10.1189/jlb.0409252] [PMID:  19843576]

[14]
Yamakage S, Oe Y, Sato E, et al. Myeloid cell-derived coagulation tissue factor is associated with renal tubular damage in mice fed an adenine diet. Sci Rep  2021; 11(1): 12159.
 [http://dx.doi.org/10.1038/s41598-021-91586-5] [PMID:  34108522]

[15]
Bluff JE, Brown NJ, Reed MWR, Staton CA. Tissue factor, angiogenesis and tumour progression. Breast Cancer Res  2008; 10(2): 204.
 [http://dx.doi.org/10.1186/bcr1871] [PMID:  18373885]

[16]
Hu Z. Therapeutic antibody-like immunoconjugates against tissue factor with the potential to treat angiogenesis-dependent as well as macrophage-associated human diseases. Antibodies   2018; 7(1): 8.
 [http://dx.doi.org/10.3390/antib7010008] [PMID:  31105982]

[17]
Salvi R, Péclat V, So A, Busso N. Enhanced expression of genes involved in coagulation and fibrinolysis in murine arthritis. Arthritis Res Ther  2000; 2(6): 504-12.
 [http://dx.doi.org/10.1186/ar132] [PMID:  11056680]

[18]
Cole M, Bromberg M. Tissue factor as a novel target for treatment of breast cancer. Oncologist  2013; 18(1): 14-8.
 [http://dx.doi.org/10.1634/theoncologist.2012-0322] [PMID:  23287882]

[19]
Butenas S. Tissue factor structure and function. Scientifica   2012; 2012: 1-15.
 [http://dx.doi.org/10.6064/2012/964862] [PMID:  24278763]

[20]
Kamikubo Y, Mendolicchio GL, Zampolli A, et al. Selective factor VIII activation by the tissue factor–factor VIIa–factor Xa complex. Blood  2017; 130(14): 1661-70.
 [http://dx.doi.org/10.1182/blood-2017-02-767079] [PMID:  28729433]

[21]
Lopes-Bezerra LM, Filler SG. Endothelial cells, tissue factor and infectious diseases. Braz J Med Biol Res  2003; 36(8): 987-91.
 [http://dx.doi.org/10.1590/S0100-879X2003000800004] [PMID:  12886452]

[22]
Dahlbäck B, Villoutreix BO. Regulation of blood coagulation by the protein C anticoagulant pathway: Novel insights into structure-function relationships and molecular recognition. Arterioscler Thromb Vasc Biol  2005; 25(7): 1311-20.
 [http://dx.doi.org/10.1161/01.ATV.0000168421.13467.82] [PMID:  15860736]

[23]
Shouman MM, Abdelsalam RM, Tawfick MM, Kenawy SA, El-Naa MM. Antisense tissue factor oligodeoxynucleotides protected diethyl nitrosamine/carbon tetrachloride-induced liver fibrosis through toll like receptor4-tissue factor-protease activated receptor1 pathway. Front Pharmacol  2021; 12: 676608.
 [http://dx.doi.org/10.3389/fphar.2021.676608] [PMID:  34045968]

[24]
Rao LVM, Pendurthi UR. Tissue factor-factor VIIa signaling. Arterioscler Thromb Vasc Biol  2005; 25(1): 47-56.
 [http://dx.doi.org/10.1161/01.ATV.0000151624.45775.13] [PMID:  15569823]

[25]
Thulin Å, Ringvall M, Dimberg A, et al. Activated platelets provide a functional microenvironment for the antiangiogenic fragment of histidine-rich glycoprotein. Mol Cancer Res  2009; 7(11): 1792-802.
 [http://dx.doi.org/10.1158/1541-7786.MCR-09-0094] [PMID:  19903770]

[26]
Yang Y, Cao Y. Eds The impact of VEGF on cancer metastasis and systemic disease Seminars in Cancer Biology. Amsterdam: Elsevier 2022.

[27]
López-Pedrera C, Barbarroja N, Dorado G, Siendones E, Velasco F. Tissue factor as an effector of angiogenesis and tumor progression in hematological malignancies. Leukemia  2006; 20(8): 1331-40.
 [http://dx.doi.org/10.1038/sj.leu.2404264] [PMID:  16728982]

[28]
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): 1734-41.
 [http://dx.doi.org/10.1182/blood-2004-05-2042] [PMID:  15494427]

[29]
Rickles FR, Shoji M, Abe K. The role of the hemostatic system in tumor growth, metastasis, and angiogenesis: Tissue factor is a bifunctional molecule capable of inducing both fibrin deposition and angiogenesis in cancer. Int J Hematol  2001; 73(2): 145-50.
 [http://dx.doi.org/10.1007/BF02981930] [PMID:  11372724]

[30]
Kohli S, Shahzad K, Jouppila A, Holthöfer H, Isermann B, Lassila R. Thrombosis and inflammation-a dynamic interplay and the role of glycosaminoglycans and activated protein C. Front Cardiovasc Med  2022; 9: 866751.
 [http://dx.doi.org/10.3389/fcvm.2022.866751] [PMID:  35433860]

[31]
Witkowski M, Weithauser A, Tabaraie T, et al. Micro–RNA-126 reduces the blood thrombogenicity in diabetes mellitus via targeting of tissue factor. Arterioscler Thromb Vasc Biol  2016; 36(6): 1263-71.
 [http://dx.doi.org/10.1161/ATVBAHA.115.306094] [PMID:  27127202]

[32]
Borensztajn K, Von Der Thüsen JH, Peppelenbosch MP, Spek CA. The coagulation factor Xa/protease activated receptor-2 axis in the progression of liver fibrosis: A multifaceted paradigm. J Cell Mol Med  2010; 14(1-2): 143-53.
 [http://dx.doi.org/10.1111/j.1582-4934.2009.00980.x] [PMID:  19968736]

[33]
Oh H, Park HE, Song MS, Kim H, Baek JH. The therapeutic potential of anticoagulation in organ fibrosis. Front Med  2022; 9: 866746.
 [http://dx.doi.org/10.3389/fmed.2022.866746] [PMID:  35652066]

[34]
Pant A, Kopec AK, Luyendyk JP. Role of the blood coagulation cascade in hepatic fibrosis. Am J Physiol Gastrointest Liver Physiol  2018; 315(2): G171-6.
 [http://dx.doi.org/10.1152/ajpgi.00402.2017] [PMID:  29723040]

[35]
Fiorucci S, Antonelli E, Distrutti E, et al. PAR1 antagonism protects against experimental liver fibrosis. Role of proteinase receptors in stellate cell activation. Hepatology  2004; 39(2): 365-75.
 [http://dx.doi.org/10.1002/hep.20054] [PMID:  14767989]

[36]
Scotton CJ, Krupiczojc MA, Königshoff M, et al. Increased local expression of coagulation factor X contributes to the fibrotic response in human and murine lung injury. J Clin Invest  2009; 119(9): 2550-63.
 [http://dx.doi.org/10.1172/JCI33288] [PMID:  19652365]

[37]
Bautista-Vargas M, Bonilla-Abadía F, Cañas CA. Potential role for tissue factor in the pathogenesis of hypercoagulability associated with in COVID-19. J Thromb Thrombolysis  2020; 50(3): 479-83.
 [http://dx.doi.org/10.1007/s11239-020-02172-x] [PMID:  32519164]

[38]
Isada A, Konno S, Hizawa N, et al. A functional polymorphism (−603A → G) in the tissue factor gene promoter is associated with adult-onset asthma. J Hum Genet  2010; 55(3): 167-74.
 [http://dx.doi.org/10.1038/jhg.2010.4] [PMID:  20150920]

[39]
McNamara CA, Sarembock IJ, Bachhuber BG, Stouffer GA, Ragosta M, Barry W. Eds. Thrombin and vascular smooth muscle cell proliferation: Implications for atherosclerosis and restenosis.Seminars in thrombosis and hemostasis. Semin Thromb Hemost  1996; 22(2): 139-44.

[40]
Kral JB, Schrottmaier WC, Salzmann M, Assinger A. Platelet interaction with innate immune cells. Transfus Med Hemother  2016; 43(2): 78-88.
 [http://dx.doi.org/10.1159/000444807] [PMID:  27226790]

[41]
Niculae CM, Hristea A, Moroti R. Mechanisms of COVID-19 Associated pulmonary thrombosis: A narrative review. Biomedicines  2023; 11(3): 929.
 [http://dx.doi.org/10.3390/biomedicines11030929] [PMID:  36979908]

[42]
Witkowski M, Landmesser U, Rauch U. Tissue factor as a link between inflammation and coagulation. Trends Cardiovasc Med  2016; 26(4): 297-303.
 [http://dx.doi.org/10.1016/j.tcm.2015.12.001] [PMID:  26877187]

[43]
Krikun G, Schatz F, Mackman N, Guller S, Demopoulos R, Lockwood CJ. Regulation of tissue factor gene expression in human endometrium by transcription factors Sp1 and Sp3. Mol Endocrinol  2000; 14(3): 393-400.
 [http://dx.doi.org/10.1210/mend.14.3.0430] [PMID:  10707957]

[44]
Egorina EM, Sovershaev TA, Hansen JB, Sovershaev MA. BMP-2 inhibits TF expression in human monocytes by shutting down MAPK signaling and AP-1 transcriptional activity. Thromb Res  2012; 129(4): e106-11.
 [http://dx.doi.org/10.1016/j.thromres.2011.10.024] [PMID:  22119392]

[45]
Sun L, Liu Y, Lin S, et al. Early growth response gene-1 and hypoxia-inducible factor-1α affect tumor metastasis via regulation of tissue factor. Acta Oncol  2013; 52(4): 842-51.
 [http://dx.doi.org/10.3109/0284186X.2013.705890] [PMID:  23409769]

[46]
Villard AV, Genna A, Gilles C. Abstract 6336: Regulation of tissue factor dependent procoagulant properties by CD44: Implication for metastasis of breast tumor cells. Cancer Res  2022; 82(12_Supplement)(Suppl.): 6336.
 [http://dx.doi.org/10.1158/1538-7445.AM2022-6336]

[47]
Moll T, Czyz M, Holzmüller H, et al. Regulation of the tissue factor promoter in endothelial cells. Binding of NF κ B-, AP-1-, and Sp1-like transcription factors. J Biol Chem  1995; 270(8): 3849-57.
 [http://dx.doi.org/10.1074/jbc.270.8.3849] [PMID:  7876129]

[48]
Parry GCN, Mackman N. Transcriptional regulation of tissue factor expression in human endothelial cells. Arterioscler Thromb Vasc Biol  1995; 15(5): 612-21.
 [http://dx.doi.org/10.1161/01.ATV.15.5.612] [PMID:  7749875]

[49]
Stojkovic S, Kaun C, Basilio J, et al. Tissue factor is induced by interleukin-33 in human endothelial cells: A new link between coagulation and inflammation. Sci Rep  2016; 6(1): 25171.
 [http://dx.doi.org/10.1038/srep25171] [PMID:  27142573]

[50]
Kamimura M, Viedt C, Dalpke A, et al. Interleukin-10 suppresses tissue factor expression in lipopolysaccharide-stimulated macrophages via inhibition of Egr-1 and a serum response element/MEK-ERK1/2 pathway. Circ Res  2005; 97(4): 305-13.
 [http://dx.doi.org/10.1161/01.RES.0000177893.24574.13] [PMID:  16037570]

[51]
Toltl LJ, Beaudin S, Liaw PC. Activated protein C up-regulates IL-10 and inhibits tissue factor in blood monocytes. J Immunol  2008; 181(3): 2165-73.
 [http://dx.doi.org/10.4049/jimmunol.181.3.2165] [PMID:  18641355]

[52]
Del Prete G, De Carli M, Lammel RM, D’Elios MM, Daniel KC, Giusti B, et al. Th1 and Th2 T-helper cells exert opposite regulatory effects on procoagulant activity and tissue factor production by human monocytes. Blood  1995; 86(1): 250-7.

[53]
Kontomanolis EN, Kalagasidou S, Fasoulakis Z. MicroRNAs as potential serum biomarkers for early detection of ectopic pregnancy. Cureus  2018; 10(3): e2344.
 [http://dx.doi.org/10.7759/cureus.2344] [PMID:  29796356]

[54]
Bartel DP. MicroRNAs: Target recognition and regulatory functions. Cell  2009; 136(2): 215-33.
 [http://dx.doi.org/10.1016/j.cell.2009.01.002] [PMID:  19167326]

[55]
Zhang X, Yu H, Lou JR, et al. MicroRNA-19 (miR-19) regulates tissue factor expression in breast cancer cells. J Biol Chem  2011; 286(2): 1429-35.
 [http://dx.doi.org/10.1074/jbc.M110.146530] [PMID:  21059650]

[56]
Teruel R, Pérez-Sánchez C, Corral J, et al. Identification of miRNAs as potential modulators of tissue factor expression in patients with systemic lupus erythematosus and antiphospholipid syndrome. J Thromb Haemost  2011; 9(10): 1985-92.
 [http://dx.doi.org/10.1111/j.1538-7836.2011.04451.x] [PMID:  21794077]

[57]
Li S, Ren J, Xu N, et al. MicroRNA-19b functions as potential anti-thrombotic protector in patients with unstable angina by targeting tissue factor. J Mol Cell Cardiol  2014; 75: 49-57.
 [http://dx.doi.org/10.1016/j.yjmcc.2014.06.017] [PMID:  24998411]

[58]
Balia C, Giordano M, Scalise V, et al. miR-19a and miR-20a and tissue factor expression in activated human peripheral blood mononuclear cells. Thrombosis  2017; 2017: 1-6.
 [http://dx.doi.org/10.1155/2017/1076397] [PMID:  29214079]

[59]
Yu G, li H, Wang X, et al. MicroRNA-19a targets tissue factor to inhibit colon cancer cells migration and invasion. Mol Cell Biochem  2013; 380(1-2): 239-47.
 [http://dx.doi.org/10.1007/s11010-013-1679-6] [PMID:  23666757]

[60]
Witkowski M, Tabaraie T, Steffens D, et al. MicroRNA-19a contributes to the epigenetic regulation of tissue factor in diabetes. Cardiovasc Diabetol  2018; 17(1): 34.
 [http://dx.doi.org/10.1186/s12933-018-0678-z] [PMID:  29477147]

[61]
Zhang R, Lu S, Yang X, et al. miR-19a-3p downregulates tissue factor and functions as a potential therapeutic target for sepsis-induced disseminated intravascular coagulation. Biochem Pharmacol  2021; 192: 114671.
 [http://dx.doi.org/10.1016/j.bcp.2021.114671] [PMID:  34246626]

[62]
Eisenreich A, Bogdanov VY, Zakrzewicz A, et al. Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor in human endothelial cells. Circ Res  2009; 104(5): 589-99.
 [http://dx.doi.org/10.1161/CIRCRESAHA.108.183905] [PMID:  19168442]

[63]
Eisenreich A, Rauch U. Regulation of the tissue factor isoform expression and thrombogenicity of HMEC-1 by miR-126 and miR-19a. Cell Biol Res Ther  2013; 2: 1-2.

[64]
Giannella A, Radu CM, Franco L, et al. Circulating levels and characterization of microparticles in patients with different degrees of glucose tolerance. Cardiovasc Diabetol  2017; 16(1): 118.
 [http://dx.doi.org/10.1186/s12933-017-0600-0] [PMID:  28927403]

[65]
Chuang TD, Luo X, Panda H, Chegini N. miR-93/106b and their host gene, MCM7, are differentially expressed in leiomyomas and functionally target F3 and IL-8. Mol Endocrinol  2012; 26(6): 1028-42.
 [http://dx.doi.org/10.1210/me.2012-1075] [PMID:  22556343]

[66]
D’Asti E, Huang A, Kool M, et al. Tissue factor regulation by miR-520g in primitive neuronal brain tumor cells: A possible link between oncomirs and the vascular tumor microenvironment. Am J Pathol  2016; 186(2): 446-59.
 [http://dx.doi.org/10.1016/j.ajpath.2015.10.020] [PMID:  26687818]

[67]
Li S, Yuan L, Su L, et al. Decreased miR 92a 3p expression potentially mediates the pro angiogenic effects of oxidative stress activated endothelial cell derived exosomes by targeting tissue factor. Int J Mol Med  2020; 46(5): 1886-98.
 [http://dx.doi.org/10.3892/ijmm.2020.4713] [PMID:  32901851]

[68]
Sahu A, Jha PK, Prabhakar A, et al. MicroRNA-145 impedes thrombus formation via targeting tissue factor in venous thrombosis. EBioMedicine  2017; 26: 175-86.
 [http://dx.doi.org/10.1016/j.ebiom.2017.11.022] [PMID:  29217135]

[69]
Li S, Chen H, Ren J, et al. MicroRNA-223 inhibits tissue factor expression in vascular endothelial cells. Atherosclerosis  2014; 237(2): 514-20.
 [http://dx.doi.org/10.1016/j.atherosclerosis.2014.09.033] [PMID:  25463083]

[70]
Collier MEW, Ambrose AR, Goodall AH. Does hsa-miR-223-3p from platelet-derived extracellular vesicles regulate tissue factor expression in monocytic cells? Platelets  2022; 33(7): 1031-42.
 [http://dx.doi.org/10.1080/09537104.2022.2027903] [PMID:  35132909]

[71]
Tian J, Adams MJ, Tay JWT, et al. Estradiol-responsive miR-365a-3p interacts with tissue factor 3' UTR to modulate tissue factor-initiated thrombin generation. Thromb Haemost  2021; 121(11): 1483-96.
 [http://dx.doi.org/10.1055/a-1382-9983] [PMID:  33540457]

[72]
Witkowski M, Witkowski M, Saffarzadeh M, et al. Vascular miR-181b controls tissue factor-dependent thrombogenicity and inflammation in type 2 diabetes. Cardiovasc Diabetol  2020; 19(1): 20.
 [http://dx.doi.org/10.1186/s12933-020-0993-z] [PMID:  32066445]

[73]
Ali HO, Arroyo AB, González-Conejero R, et al. The role of microRNA-27a/b and microRNA-494 in estrogen-mediated downregulation of tissue factor pathway inhibitor α J Thromb Haemost  2016; 14(6): 1226-37.
 [http://dx.doi.org/10.1111/jth.13321] [PMID:  26999003]

[74]
Jankowska KI, Sauna ZE, Atreya CD. Role of microRNAs in hemophilia and thrombosis in humans. Int J Mol Sci  2020; 21(10): 3598.
 [http://dx.doi.org/10.3390/ijms21103598] [PMID:  32443696]

[75]
Cottrell GS, Coelho AM, Bunnett NW, Bunnett NW. Protease-activated receptors: The role of cell-surface proteolysis in signalling. Essays Biochem  2002; 38: 169-83.
 [http://dx.doi.org/10.1042/bse0380169] [PMID:  12463169]

[76]
Coughlin SR. Thrombin signalling and protease-activated receptors. Nature  2000; 407(6801): 258-64.
 [http://dx.doi.org/10.1038/35025229] [PMID:  11001069]

[77]
Zigler M, Kamiya T, Brantley EC, Villares GJ, Bar-Eli M. PAR-1 and thrombin: The ties that bind the microenvironment to melanoma metastasis. Cancer Res  2011; 71(21): 6561-6.
 [http://dx.doi.org/10.1158/0008-5472.CAN-11-1432] [PMID:  22009534]

[78]
Villares GJ, Zigler M, Bar-Eli M. The emerging role of the thrombin receptor (PAR-1) in melanoma metastasis--a possible therapeutic target. Oncotarget  2011; 2(1-2): 8-17.
 [http://dx.doi.org/10.18632/oncotarget.211] [PMID:  21378407]

[79]
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   2000; 97(10): 5255-60.
 [http://dx.doi.org/10.1073/pnas.97.10.5255] [PMID:  10805786]

[80]
Dorfleutner A, Ruf W. Regulation of tissue factor cytoplasmic domain phosphorylation by palmitoylation. Blood  2003; 102(12): 3998-4005.
 [http://dx.doi.org/10.1182/blood-2003-04-1149] [PMID:  12920028]

[81]
Ahamed J, Ruf W. Protease-activated receptor 2-dependent phosphorylation of the tissue factor cytoplasmic domain. J Biol Chem  2004; 279(22): 23038-44.
 [http://dx.doi.org/10.1074/jbc.M401376200] [PMID:  15039423]

[82]
Rydén L, Grabau D, Schaffner F, Jönsson PE, Ruf W, Belting M. Evidence for tissue factor phosphorylation and its correlation with protease-activated receptor expression and the prognosis of primary breast cancer. Int J Cancer  2010; 126(10): 2330-40.
 [PMID:  19795460]

[83]
Belting M, Dorrell MI, Sandgren S, et al. Regulation of angiogenesis by tissue factor cytoplasmic domain signaling. Nat Med  2004; 10(5): 502-9.
 [http://dx.doi.org/10.1038/nm1037] [PMID:  15098027]

[84]
Hoffman M. Ed The tissue factor pathway and wound healing Semin Thromb Hemost.  Thieme Medical Publishers 2018; 44: pp. (2)142-50.

[85]
Chen J, Kasper M, Heck T, et al. Tissue factor as a link between wounding and tissue repair. Diabetes  2005; 54(7): 2143-54.
 [http://dx.doi.org/10.2337/diabetes.54.7.2143] [PMID:  15983216]

[86]
Mercer PF, Chambers RC. Coagulation and coagulation signalling in fibrosis. Biochim Biophys Acta Mol Basis Dis  2013; 1832(7): 1018-27.
 [http://dx.doi.org/10.1016/j.bbadis.2012.12.013]

[87]
Gabazza EC, Taguchi O, Tamaki S, et al. Thrombin in the airways of asthmatic patients. Lung  1999; 177(4): 253-62.
 [http://dx.doi.org/10.1007/PL00007645] [PMID:  10384063]

[88]
Chambers RC, Leoni P, Blanc-Brude OP, Wembridge DE, Laurent GJ. Thrombin is a potent inducer of connective tissue growth factor production via proteolytic activation of protease-activated receptor-1. J Biol Chem  2000; 275(45): 35584-91.
 [http://dx.doi.org/10.1074/jbc.M003188200] [PMID:  10952976]

[89]
Frazier K, Williams S, Kothapalli D, Klapper H, Grotendorst GR. Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connective tissue growth factor. J Invest Dermatol  1996; 107(3): 404-11.
 [http://dx.doi.org/10.1111/1523-1747.ep12363389] [PMID:  8751978]

[90]
Keglowich LF, Borger P. The three A’s in asthma–airway smooth muscle, airway remodeling & angiogenesis. Open Respir Med J  2015; 9(1): 70-80.
 [http://dx.doi.org/10.2174/1874306401509010070] [PMID:  26106455]

[91]
Cibi DM, Sandireddy R, Bogireddi H, et al. Cardiac tissue factor regulates inflammation, hypertrophy, and heart failure in mouse model of type 1 diabetes. Diabetes  2021; 70(9): 2131-46.
 [http://dx.doi.org/10.2337/db20-0719] [PMID:  34155039]

[92]
Steffel J, Lüscher TF, Tanner FC. Tissue factor in cardiovascular diseases: molecular mechanisms and clinical implications. Circulation  2006; 113(5): 722-31.
 [http://dx.doi.org/10.1161/CIRCULATIONAHA.105.567297] [PMID:  16461845]

[93]
Glembotski CC, Irons CE, Krown KA, Murray SF, Sprenkle AB, Sei CA. Myocardial alpha-thrombin receptor activation induces hypertrophy and increases atrial natriuretic factor gene expression. J Biol Chem  1993; 268(27): 20646-52.
 [http://dx.doi.org/10.1016/S0021-9258(20)80773-X] [PMID:  8397212]

[94]
Sabri A, Muske G, Zhang H, et al. Signaling properties and functions of two distinct cardiomyocyte protease-activated receptors. Circ Res  2000; 86(10): 1054-61.
 [http://dx.doi.org/10.1161/01.RES.86.10.1054] [PMID:  10827135]

[95]
Antoniak S, Pawlinski R, Mackman N. Protease-activated receptors and myocardial infarction. IUBMB Life  2011; 63(6): 383-9.
 [http://dx.doi.org/10.1002/iub.441] [PMID:  21438116]

[96]
Demetz G, Ott I. The interface between inflammation and coagulation in cardiovascular disease. Int J Inflam  2012; 2012: 860301.
 [http://dx.doi.org/10.1155/2012/860301]

[97]
Mackman N. Role of tissue factor in hemostasis, thrombosis, and vascular development. Arterioscler Thromb Vasc Biol  2004; 24(6): 1015-22.
 [http://dx.doi.org/10.1161/01.ATV.0000130465.23430.74] [PMID:  15117736]

[98]
Mackman N, Tilley RE, Key NS. Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis. Arterioscler Thromb Vasc Biol  2007; 27(8): 1687-93.
 [http://dx.doi.org/10.1161/ATVBAHA.107.141911] [PMID:  17556654]

[99]
FitzGerald ES, Chen Y, Fitzgerald KA, Jamieson AM. Lung epithelial cell transcriptional regulation as a factor in COVID-19–associated coagulopathies. Am J Respir Cell Mol Biol  2021; 64(6): 687-97.
 [http://dx.doi.org/10.1165/rcmb.2020-0453OC] [PMID:  33740387]

[100]
Nascimento Conde J, Schutt WR, Gorbunova EE, Mackow ER. Recombinant ACE2 expression is required for SARS-CoV-2 to infect primary human endothelial cells and induce inflammatory and procoagulative responses. MBio  2020; 11(6): e03185-20.
 [http://dx.doi.org/10.1128/mBio.03185-20] [PMID:  33310781]

[101]
Amraei R, Xia C, Olejnik J, et al. Extracellular vimentin is an attachment factor that facilitates SARS-CoV-2 entry into human endothelial cells. Proc Natl Acad Sci   2022; 119(6): e2113874119.
 [http://dx.doi.org/10.1073/pnas.2113874119] [PMID:  35078919]

[102]
Ollivier V, Bentolila S, Chabbat J, Hakim J, de Prost D. Tissue factor-dependent vascular endothelial growth factor production by human fibroblasts in response to activated factor VII. Blood  1998; 91(8): 2698-703.
 [http://dx.doi.org/10.1182/blood.V91.8.2698.2698_2698_2703] [PMID:  9531578]

[103]
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): 1241-53.
 [http://dx.doi.org/10.1083/jcb.140.5.1241] [PMID:  9490735]

[104]
Hisada Y, Mackman N. Eds. Tissue factor and cancer: regulation, tumor growth, and metastasis. Semin Thromb Hemost.  New York: Thieme Medical Publishers 2019; 45: pp. (4)385-95.

[105]
Yang Y, Stang A, Schweickert PG, et al. Thrombin signaling promotes pancreatic adenocarcinoma through PAR-1–dependent immune evasion. Cancer Res  2019; 79(13): 3417-30.
 [http://dx.doi.org/10.1158/0008-5472.CAN-18-3206] [PMID:  31048498]

[106]
Markiewski MM, DeAngelis RA, Benencia F, et al. Modulation of the antitumor immune response by complement. Nat Immunol  2008; 9(11): 1225-35.
 [http://dx.doi.org/10.1038/ni.1655] [PMID:  18820683]

[107]
Rao B, Gao Y, Huang J, et al. Mutations of p53 and K-ras correlate TF expression in human colorectal carcinomas: TF downregulation as a marker of poor prognosis. Int J Colorectal Dis  2011; 26(5): 593-601.
 [http://dx.doi.org/10.1007/s00384-011-1164-1] [PMID:  21404058]

[108]
Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov  2005; 4(12): 988-1004.
 [http://dx.doi.org/10.1038/nrd1902] [PMID:  16341064]

[109]
Vanhaesebroeck B, Guillermet-Guibert J, Graupera M, Bilanges B. The emerging mechanisms of isoform-specific PI3K signalling. Nat Rev Mol Cell Biol  2010; 11(5): 329-41.
 [http://dx.doi.org/10.1038/nrm2882] [PMID:  20379207]

[110]
Nishikawa R, Ji XD, Harmon RC, et al. A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity. Proc Natl Acad Sci   1994; 91(16): 7727-31.
 [http://dx.doi.org/10.1073/pnas.91.16.7727] [PMID:  8052651]

[111]
Åberg 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): 141-8.
 [http://dx.doi.org/10.1016/j.thromres.2010.11.015] [PMID:  21168190]

[112]
Åberg M, Wickström M, Siegbahn A. Simvastatin induces apoptosis in human breast cancer cells in a NFκB-dependent manner and abolishes the anti-apoptotic signaling of TF/FVIIa and TF/FVIIa/FXa. Thromb Res  2008; 122(2): 191-202.
 [http://dx.doi.org/10.1016/j.thromres.2007.09.017] [PMID:  18031796]

[113]
Versteeg HH, Arnold Spek C, Richel DJ, Peppelenbosch MP. Coagulation factors VIIa and Xa inhibit apoptosis and anoikis. Oncogene  2004; 23(2): 410-7.
 [http://dx.doi.org/10.1038/sj.onc.1207066] [PMID:  14724569]

[114]
Versteeg HH, Spek CA, Slofstra SH, Diks SH, Richel DJ, Peppelenbosch MP. FVIIa:TF induces cell survival via G12/G13-dependent Jak/STAT activation and BclXL production. Circ Res  2004; 94(8): 1032-40.
 [http://dx.doi.org/10.1161/01.RES.0000125625.18597.AD] [PMID:  15016732]

[115]
Sorensen BB, Vijaya Mohan Rao L, Tornehave D, Gammeltoft S, Petersen LC. Antiapoptotic effect of coagulation factor VIIa. Blood  2003; 102(5): 1708-15.
 [http://dx.doi.org/10.1182/blood-2003-01-0157] [PMID:  12738672]

[116]
Thorpe LM, Yuzugullu H, Zhao JJ. PI3K in cancer: Divergent roles of isoforms, modes of activation and therapeutic targeting. Nat Rev Cancer  2015; 15(1): 7-24.
 [http://dx.doi.org/10.1038/nrc3860] [PMID:  25533673]

[117]
Hanker AB, Kaklamani V, Arteaga CL. Challenges for the clinical development of PI3K inhibitors: Strategies to improve their impact in solid tumors. Cancer Discov  2019; 9(4): 482-91.
 [http://dx.doi.org/10.1158/2159-8290.CD-18-1175] [PMID:  30867161]

[118]
Jiang BH, Liu LZ. AKT signaling in regulating angiogenesis. Curr Cancer Drug Targets  2008; 8(1): 19-26.
 [http://dx.doi.org/10.2174/156800908783497122] [PMID:  18288940]

[119]
Toschi A, Lee E, Gadir N, Ohh M, Foster DA. Differential dependence of hypoxia-inducible factors 1α and 2α on mTORC1 and mTORC2. J Biol Chem  2008; 283(50): 34495-9.
 [http://dx.doi.org/10.1074/jbc.C800170200] [PMID:  18945681]

[120]
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): 3029-37.
 [http://dx.doi.org/10.1182/blood-2003-10-3417] [PMID:  15070680]

[121]
Schaffner F, Versteeg HH, Schillert A, et al. Cooperation of tissue factor cytoplasmic domain and PAR2 signaling in breast cancer development. Blood  2010; 116(26): 6106-13.
 [http://dx.doi.org/10.1182/blood-2010-06-289314] [PMID:  20861457]

[122]
Unruh D, Turner K, Srinivasan R, et al. Alternatively spliced tissue factor contributes to tumor spread and activation of coagulation in pancreatic ductal adenocarcinoma. Int J Cancer  2014; 134(1): 9-20.
 [http://dx.doi.org/10.1002/ijc.28327] [PMID:  23754313]

[123]
Reinke JM, Sorg H. Wound repair and regeneration. Eur Surg Res  2012; 49(1): 35-43.
 [http://dx.doi.org/10.1159/000339613] [PMID:  22797712]

[124]
Browder T, Folkman J, Pirie-Shepherd S. The hemostatic system as a regulator of angiogenesis. J Biol Chem  2000; 275(3): 1521-4.
 [http://dx.doi.org/10.1074/jbc.275.3.1521] [PMID:  10636838]

[125]
Martino MM, Briquez PS, Ranga A, Lutolf MP, Hubbell JA. Heparin-binding domain of fibrin(ogen) binds growth factors and promotes tissue repair when incorporated within a synthetic matrix. Proc Natl Acad Sci   2013; 110(12): 4563-8.
 [http://dx.doi.org/10.1073/pnas.1221602110] [PMID:  23487783]

[126]
Sahni A, Odrljin T, Francis CW. Binding of basic fibroblast growth factor to fibrinogen and fibrin. J Biol Chem  1998; 273(13): 7554-9.
 [http://dx.doi.org/10.1074/jbc.273.13.7554] [PMID:  9516457]

[127]
Sahni A, Francis CW. Vascular endothelial growth factor binds to fibrinogen and fibrin and stimulates endothelial cell proliferation. Blood  2000; 96(12): 3772-8.
 [http://dx.doi.org/10.1182/blood.V96.12.3772] [PMID:  11090059]

[128]
Albrektsen T, Sørensen BB, Hjortø GM, Fleckner J, Rao LVM, Petersen LC. Transcriptional program induced by factor VIIa-tissue factor, PAR1 and PAR2 in MDA-MB-231 cells. J Thromb Haemost  2007; 5(8): 1588-97.
 [http://dx.doi.org/10.1111/j.1538-7836.2007.02603.x] [PMID:  17470200]

[129]
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): 4461-7.
 [PMID:  9766679]

[130]
Camerer E, Røttingen JA, Gjernes E, et al. Coagulation factors VIIa and Xa induce cell signaling leading to up-regulation of the egr-1 gene. J Biol Chem  1999; 274(45): 32225-33.
 [http://dx.doi.org/10.1074/jbc.274.45.32225] [PMID:  10542260]

[131]
Hu L, Xia L, Zhou H, et al. TF/FVIIa/PAR2 promotes cell proliferation and migration via PKCα and ERK-dependent c-Jun/AP-1 pathway in colon cancer cell line SW620. Tumour Biol  2013; 34(5): 2573-81.
 [http://dx.doi.org/10.1007/s13277-013-0803-2] [PMID:  23616010]

[132]
Wu B, Zhou H, Hu L, Mu Y, Wu Y. Involvement of PKCα activation in TF/VIIa/PAR2-induced proliferation, migration, and survival of colon cancer cell SW620. Tumour Biol  2013; 34(2): 837-46.
 [http://dx.doi.org/10.1007/s13277-012-0614-x] [PMID:  23233043]

[133]
Hassan N, Efing J, Kiesel L, Bendas G, Götte M. The tissue factor pathway in cancer: Overview and role of heparan sulfate proteoglycans. Cancers   2023; 15(5): 1524.
 [http://dx.doi.org/10.3390/cancers15051524] [PMID:  36900315]

[134]
Abe K, Shoji M, Chen J, et al. Regulation of vascular endothelial growth factor production and angiogenesis by the cytoplasmic tail of tissue factor. Proc Natl Acad Sci   1999; 96(15): 8663-8.
 [http://dx.doi.org/10.1073/pnas.96.15.8663] [PMID:  10411932]

[135]
Guo YJ, Pan WW, Liu SB, Shen ZF, Xu Y, Hu LL. ERK/MAPK signalling pathway and tumorigenesis. Exp Ther Med  2020; 19(3): 1997-2007.
 [PMID:  32104259]

[136]
Zhang J, Ding J, Zhang X, Shao X, Hao Z. Regulation of vascular endothelial growth factor (VEGF) production and angiogenesis by tissue factor (TF) in SGC-7901 gastric cancer cells. Cancer Biol Ther  2005; 4(7): 769-72.
 [http://dx.doi.org/10.4161/cbt.4.7.1871] [PMID:  15846107]

[137]
Menachery VD, Gralinski LE. Coagulation and wound repair during COVID-19. J Heart Lung Transplant  2021; 40(10): 1076-81.
 [http://dx.doi.org/10.1016/j.healun.2021.06.006] [PMID:  34334300]

[138]
Guo S, DiPietro LA. Factors affecting wound healing. J Dent Res  2010; 89(3): 219-29.
 [http://dx.doi.org/10.1177/0022034509359125] [PMID:  20139336]

[139]
Chen J, Bierhaus A, Schiekofer S, et al. Tissue factor: A receptor involved in the control of cellular properties, including angiogenesis. Thromb Haemost  2001; 86(7): 334-45.
 [http://dx.doi.org/10.1055/s-0037-1616231] [PMID:  11487022]

[140]
Luther T, Mackman N. Tissue factor in the heart. Multiple roles in hemostasis, thrombosis, and inflammation. Trends Cardiovasc Med  2001; 11(8): 307-12.
 [http://dx.doi.org/10.1016/S1050-1738(01)00129-3] [PMID:  11728878]

[141]
Peppelenbosch M, Versteeg HH. Cell biology of tissue factor, an unusual member of the cytokine receptor family. Trends Cardiovasc Med  2001; 11(8): 335-9.
 [http://dx.doi.org/10.1016/S1050-1738(01)00137-2] [PMID:  11728883]

[142]
Sen CK, Roy S. Redox signals in wound healing. Biochim Biophys Acta, Gen Subj  2008; 1780(11): 1348-61.
 [http://dx.doi.org/10.1016/j.bbagen.2008.01.006]

[143]
Herkert O, Djordjevic T, Belaiba RS, Görlach A. Insights into the redox control of blood coagulation: Role of vascular NADPH oxidase-derived reactive oxygen species in the thrombogenic cycle. Antioxid Redox Signal  2004; 6(4): 765-76.
 [http://dx.doi.org/10.1089/1523086041361695] [PMID:  15242558]

[144]
Zhao J, Jiang T, Li P, et al. Tissue factor promotes airway pathological features through epithelial-mesenchymal transition of bronchial epithelial cells in mice with house dust mite-induced asthma. Int Immunopharmacol  2021; 97: 107690.
 [http://dx.doi.org/10.1016/j.intimp.2021.107690] [PMID:  33940323]

[145]
Trompette A, Divanovic S, Visintin A, et al. Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein. Nature  2009; 457(7229): 585-8.
 [http://dx.doi.org/10.1038/nature07548] [PMID:  19060881]

[146]
Mitchel JA, Antoniak S, Lee JH, et al. IL-13 augments compressive stress–induced tissue factor expression in human airway epithelial cells. Am J Respir Cell Mol Biol  2016; 54(4): 524-31.
 [http://dx.doi.org/10.1165/rcmb.2015-0252OC] [PMID:  26407210]

[147]
de Halleux S, Stura E, VanderElst L, Carlier V, Jacquemin M, Saint-Remy JM. Three-dimensional structure and IgE-binding properties of mature fully active Der p 1, a clinically relevant major allergen. J Allergy Clin Immunol  2006; 117(3): 571-6.
 [http://dx.doi.org/10.1016/j.jaci.2005.11.032] [PMID:  16522455]

[148]
Thomas WR, Hales BJ, Smith WA. House dust mite allergens in asthma and allergy. Trends Mol Med  2010; 16(7): 321-8.
 [http://dx.doi.org/10.1016/j.molmed.2010.04.008] [PMID:  20605742]

[149]
Wan H, Winton HL, Soeller C, et al. Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions. J Clin Invest  1999; 104(1): 123-33.
 [http://dx.doi.org/10.1172/JCI5844] [PMID:  10393706]

[150]
de Boer JD, Majoor CJ, van ’t Veer C, Bel EHD, van der Poll T. Asthma and coagulation. Blood  2012; 119(14): 3236-44.
 [http://dx.doi.org/10.1182/blood-2011-11-391532] [PMID:  22262775]

[151]
Perrio MJ, Ewen D, Trevethick MA, Salmon GP, Shute JK. Fibrin formation by wounded bronchial epithelial cell layers in vitro is essential for normal epithelial repair and independent of plasma proteins. Clin Exp Allergy  2007; 37(11): 1688-700.
 [http://dx.doi.org/10.1111/j.1365-2222.2007.02829.x] [PMID:  17892513]

[152]
Bode MF, Mackman N. Protective and pathological roles of tissue factor in the heart. Hamostaseologie  2015; 35(1): 37-46.
 [http://dx.doi.org/10.5482/HAMO-14-09-0042] [PMID:  25434707]

[153]
Grover SP, Mackman N. Tissue factor in atherosclerosis and atherothrombosis. Atherosclerosis  2020; 307: 80-6.
 [http://dx.doi.org/10.1016/j.atherosclerosis.2020.06.003] [PMID:  32674807]

[154]
Bochkov VN, Mechtcheriakova D, Lucerna M, et al. Oxidized phospholipids stimulate tissue factor expression in human endothelial cells via activation of ERK/EGR-1 and Ca++/NFAT. Blood  2002; 99(1): 199-206.
 [http://dx.doi.org/10.1182/blood.V99.1.199] [PMID:  11756172]

[155]
Schecter AD, Spirn B, Rossikhina M, et al. Release of active tissue factor by human arterial smooth muscle cells. Circ Res  2000; 87(2): 126-32.
 [http://dx.doi.org/10.1161/01.RES.87.2.126] [PMID:  10903996]

[156]
Liu ML, Reilly MP, Casasanto P, McKenzie SE, Williams KJ. Cholesterol enrichment of human monocyte/macrophages induces surface exposure of phosphatidylserine and the release of biologically-active tissue factor-positive microvesicles. Arterioscler Thromb Vasc Biol  2007; 27(2): 430-5.
 [http://dx.doi.org/10.1161/01.ATV.0000254674.47693.e8] [PMID:  17158353]

[157]
Hatakeyama K, Asada Y, Marutsuka K, Sato Y, Kamikubo Y, Sumiyoshi A. Localization and activity of tissue factor in human aortic atherosclerotic lesions. Atherosclerosis  1997; 133(2): 213-9.
 [http://dx.doi.org/10.1016/S0021-9150(97)00132-9] [PMID:  9298681]

[158]
Seimon T, Tabas I. Mechanisms and consequences of macrophage apoptosis in atherosclerosis. J Lipid Res  2009; 50 (Suppl.): S382-7.
 [http://dx.doi.org/10.1194/jlr.R800032-JLR200]

[159]
Pawlinski R, Tencati M, Hampton CR, et al. Protease-activated receptor-1 contributes to cardiac remodeling and hypertrophy. Circulation  2007; 116(20): 2298-306.
 [http://dx.doi.org/10.1161/CIRCULATIONAHA.107.692764] [PMID:  17967980]

[160]
Borissoff JI, Spronk HMH, ten Cate H. The hemostatic system as a modulator of atherosclerosis. N Engl J Med  2011; 364(18): 1746-60.
 [http://dx.doi.org/10.1056/NEJMra1011670] [PMID:  21542745]

[161]
Demetz G, Ott I. The interface between inflammation and coagulation in cardiovascular disease. Int J Inflamm  2012; 2012: 1-8.
 [http://dx.doi.org/10.1155/2012/860301] [PMID:  22518344]

[162]
Vallejo JG. Role of Toll-like receptors in cardiovascular diseases. Clin Sci  2011; 121(1): 1-10.
 [http://dx.doi.org/10.1042/CS20100539] [PMID:  21413930]

[163]
Bezhaeva T, Karper J, Quax PHA, de Vries MR. The intriguing role of tlr accessory molecules in cardiovascular health and disease. Front Cardiovasc Med  2022; 9: 820962.
 [http://dx.doi.org/10.3389/fcvm.2022.820962] [PMID:  35237675]

[164]
Subramaniam S, Scharrer I. Procoagulant activity during viral infections. Front Biosci  2018; 23(6): 1060-81.
 [PMID:  28930589]

[165]
Mast AE, Wolberg AS, Gailani D, et al. SARS-CoV-2 suppresses anticoagulant and fibrinolytic gene expression in the lung. eLife  2021; 10: e64330.
 [http://dx.doi.org/10.7554/eLife.64330] [PMID:  33683204]

[166]
Subramaniam S, Kothari H, Bosmann M. Tissue factor in COVID-19-associated coagulopathy. Thromb Res  2022; 220: 35-47.
 [http://dx.doi.org/10.1016/j.thromres.2022.09.025] [PMID:  36265412]

[167]
Antoniak S, Mackman N. Multiple roles of the coagulation protease cascade during virus infection. Blood  2014; 123(17): 2605-13.
 [http://dx.doi.org/10.1182/blood-2013-09-526277] [PMID:  24632711]

[168]
Antoniak S. The coagulation system in host defense. Res Pract Thromb Haemost  2018; 2(3): 549-57.
 [http://dx.doi.org/10.1002/rth2.12109] [PMID:  30046760]

[169]
Beristain-Covarrubias N, Perez-Toledo M, Thomas MR, Henderson IR, Watson SP, Cunningham AF. Understanding infection-induced thrombosis: lessons learned from animal models. Front Immunol  2019; 10: 2569.
 [http://dx.doi.org/10.3389/fimmu.2019.02569] [PMID:  31749809]

[170]
Sumbria D, Berber E, Rouse BT. Factors affecting the tissue damaging consequences of viral infections. Front Microbiol  2019; 10: 2314.
 [http://dx.doi.org/10.3389/fmicb.2019.02314] [PMID:  31636623]

[171]
Bilaloglu S, Aphinyanaphongs Y, Jones S, Iturrate E, Hochman J, Berger JS. Thrombosis in hospitalized patients with COVID-19 in a new york city health system. JAMA  2020; 324(8): 799-801.
 [http://dx.doi.org/10.1001/jama.2020.13372] [PMID:  32702090]

[172]
Mackman N, Grover SP, Antoniak S. Tissue factor expression, extracellular vesicles, and thrombosis after infection with the respiratory viruses influenza A virus and coronavirus. J Thromb Haemost  2021; 19(11): 2652-8.
 [http://dx.doi.org/10.1111/jth.15509] [PMID:  34418279]

[173]
de Bruin S, Bos LD, van Roon MA, et al. Clinical features and prognostic factors in Covid-19: A prospective cohort study. EBioMedicine  2021; 67: 103378.
 [http://dx.doi.org/10.1016/j.ebiom.2021.103378] [PMID:  34000622]

[174]
Geisbert TW, Young HA, Jahrling PB, Davis KJ, Kagan E, Hensley LE. Mechanisms underlying coagulation abnormalities in ebola hemorrhagic fever: Overexpression of tissue factor in primate monocytes/macrophages is a key event. J Infect Dis  2003; 188(11): 1618-29.
 [http://dx.doi.org/10.1086/379724] [PMID:  14639531]

[175]
Hottz ED, Azevedo-Quintanilha IG, Palhinha L, et al. Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19. Blood  2020; 136(11): 1330-41.
 [http://dx.doi.org/10.1182/blood.2020007252] [PMID:  32678428]

[176]
Rosell A, Havervall S, von Meijenfeldt F, et al. Patients with COVID-19 have elevated levels of circulating extracellular vesicle tissue factor activity that is associated with severity and mortality—Brief report. Arterioscler Thromb Vasc Biol  2021; 41(2): 878-82.
 [http://dx.doi.org/10.1161/ATVBAHA.120.315547] [PMID:  33267656]

[177]
Houston DS. Tissue factor – a therapeutic target for thrombotic disorders. Expert Opin Ther Targets  2002; 6(2): 159-74.
 [http://dx.doi.org/10.1517/14728222.6.2.159] [PMID:  12223078]

[178]
Bayleyegn B, Adane T, Getawa S, Aynalem M, Kifle ZD. Coagulation parameters in lung cancer patients: A systematic review and meta-analysis. J Clin Lab Anal  2022; 36(7): e24550.
 [http://dx.doi.org/10.1002/jcla.24550] [PMID:  35719003]

[179]
Staton CA, Chetwood ASA, Cameron IC, Cross SS, Brown NJ, Reed MWR. The angiogenic switch occurs at the adenoma stage of the adenoma carcinoma sequence in colorectal cancer. Gut  2007; 56(10): 1426-32.
 [http://dx.doi.org/10.1136/gut.2007.125286] [PMID:  17566019]

[180]
Wu M, Chen L, Xu T, Xu B, Jiang J, Wu C. Prognostic values of tissue factor and its alternatively splice transcripts in human gastric cancer tissues. Oncotarget  2017; 8(32): 53137-45.
 [http://dx.doi.org/10.18632/oncotarget.17942] [PMID:  28881799]

[181]
Rollin J, Regina S, Gruel Y. Tumor expression of alternatively spliced tissue factor is a prognostic marker in non-small cell lung cancer. J Thromb Haemost  2010; 8(3): 607-10.
 [http://dx.doi.org/10.1111/j.1538-7836.2009.03713.x] [PMID:  19995406]

[182]
Mueller BM, Reisfeld RA, Edgington TS, Ruf W. Expression of tissue factor by melanoma cells promotes efficient hematogenous metastasis. Proc Natl Acad Sci   1992; 89(24): 11832-6.
 [http://dx.doi.org/10.1073/pnas.89.24.11832] [PMID:  1465406]

[183]
Unruh D, Mirkov S, Wray B, et al. Methylation-dependent tissue factor suppression contributes to the reduced malignancy of IDH1-mutant gliomas. Clin Cancer Res  2019; 25(2): 747-59.
 [http://dx.doi.org/10.1158/1078-0432.CCR-18-1222] [PMID:  30266764]

[184]
Hisada Y, Mackman N. Eds. Tissue factor and cancer: Regulation, tumor growth and metastasis. Semin Thromb Hemost  2019; 45(4): 385-95.

[185]
Alexander ET, Gilmour SK. Immunomodulatory role of thrombin in cancer progression. Mol Carcinog  2022; 61(6): 527-36.
 [http://dx.doi.org/10.1002/mc.23398] [PMID:  35338515]

[186]
Krisinger MJ, Goebeler V, Lu Z, et al. Thrombin generates previously unidentified C5 products that support the terminal complement activation pathway. Blood  2012; 120(8): 1717-25.
 [http://dx.doi.org/10.1182/blood-2012-02-412080] [PMID:  22802338]

[187]
Unruh D, Horbinski C. Beyond thrombosis: The impact of tissue factor signaling in cancer. J Hematol Oncol  2020; 13(1): 93.
 [http://dx.doi.org/10.1186/s13045-020-00932-z] [PMID:  32665005]

[188]
Courtney KD, Corcoran RB, Engelman JA. The PI3K pathway as drug target in human cancer. J Clin Oncol  2010; 28(6): 1075-83.
 [http://dx.doi.org/10.1200/JCO.2009.25.3641] [PMID:  20085938]

[189]
Cavenee WK. Genetics and new approaches to cancer therapy. Carcinogenesis  2002; 23(5): 683-6.
 [http://dx.doi.org/10.1093/carcin/23.5.683] [PMID:  12016138]

[190]
Lammering G, Valerie K, Lin PS, Hewit TH, Schmidt-Ullrich RK. Radiation-induced activation of a common variant of EGFR confers enhanced radioresistance. Radiother Oncol  2004; 72(3): 267-73.
 [http://dx.doi.org/10.1016/j.radonc.2004.07.004] [PMID:  15450724]

[191]
Heimberger AB, Hlatky R, Suki D, et al. Prognostic effect of epidermal growth factor receptor and EGFRvIII in glioblastoma multiforme patients. Clin Cancer Res  2005; 11(4): 1462-6.
 [http://dx.doi.org/10.1158/1078-0432.CCR-04-1737] [PMID:  15746047]

[192]
Horbinski C, Mojesky C, Kyprianou N. Live free or die: Tales of homeless (cells) in cancer. Am J Pathol  2010; 177(3): 1044-52.
 [http://dx.doi.org/10.2353/ajpath.2010.091270] [PMID:  20639456]

[193]
Rong Y, Belozerov VE, Tucker-Burden C, et al. Epidermal growth factor receptor and PTEN modulate tissue factor expression in glioblastoma through JunD/activator protein-1 transcriptional activity. Cancer Res  2009; 69(6): 2540-9.
 [http://dx.doi.org/10.1158/0008-5472.CAN-08-1547] [PMID:  19276385]

[194]
Khezri MR, Varzandeh R, Ghasemnejad-Berenji M. The probable role and therapeutic potential of the PI3K/AKT signaling pathway in SARS-CoV-2 induced coagulopathy. Cell Mol Biol Lett  2022; 27(1): 6.
 [http://dx.doi.org/10.1186/s11658-022-00308-w] [PMID:  35016612]

[195]
Magnus N, Garnier D, Rak J. Oncogenic epidermal growth factor receptor up-regulates multiple elements of the tissue factor signaling pathway in human glioma cells. Blood  2010; 116(5): 815-8.
 [http://dx.doi.org/10.1182/blood-2009-10-250639] [PMID:  20462964]

[196]
Milsom CC, Yu JL, Mackman N, et al. Tissue factor regulation by epidermal growth factor receptor and epithelial-to-mesenchymal transitions: effect on tumor initiation and angiogenesis. Cancer Res  2008; 68(24): 10068-76.
 [http://dx.doi.org/10.1158/0008-5472.CAN-08-2067] [PMID:  19074872]

[197]
Liu Y, Mueller BM. Protease-activated receptor-2 regulates vascular endothelial growth factor expression in MDA-MB-231 cells via MAPK pathways. Biochem Biophys Res Commun  2006; 344(4): 1263-70.
 [http://dx.doi.org/10.1016/j.bbrc.2006.04.005] [PMID:  16650817]

[198]
Song HB, Park KD, Kim JH, Kim DH, Yu YS, Kim JH. Tissue factor regulates tumor angiogenesis of retinoblastoma via the extracellular signal-regulated kinase pathway. Oncol Rep  2012; 28(6): 2057-62.
 [http://dx.doi.org/10.3892/or.2012.2048] [PMID:  23007470]

[199]
Qiao A, Gu F, Guo X, Zhang X, Fu L. Breast cancer-associated fibroblasts: Their roles in tumor initiation, progression and clinical applications. Front Med  2016; 10(1): 33-40.
 [http://dx.doi.org/10.1007/s11684-016-0431-5] [PMID:  26791754]

[200]
Januškevičienė I, Petrikaitė V. Heterogeneity of breast cancer: The importance of interaction between different tumor cell populations. Life Sci  2019; 239: 117009.
 [http://dx.doi.org/10.1016/j.lfs.2019.117009] [PMID:  31669239]

[201]
Soysal SD, Tzankov A, Muenst SE. Role of the tumor microenvironment in breast cancer. Pathobiology  2015; 82(3-4): 142-52.
 [http://dx.doi.org/10.1159/000430499] [PMID:  26330355]

[202]
Versteeg HH, Schaffner F, Kerver M, et al. Protease-activated receptor (PAR) 2, but not PAR1, signaling promotes the development of mammary adenocarcinoma in polyoma middle T mice. Cancer Res  2008; 68(17): 7219-27.
 [http://dx.doi.org/10.1158/0008-5472.CAN-08-0419] [PMID:  18757438]

[203]
Subramaniam S, Ogoti Y, Hernandez I, et al. A thrombin-PAR1/2 feedback loop amplifies thromboinflammatory endothelial responses to the viral RNA analogue poly(I:C). Blood Adv  2021; 5(13): 2760-74.
 [http://dx.doi.org/10.1182/bloodadvances.2021004360] [PMID:  34242391]

[204]
Guan M, Jin J, Su B, Liu WW, Lu Y. Tissue factor expression and angiogenesis in human glioma. Clin Biochem  2002; 35(4): 321-5.
 [http://dx.doi.org/10.1016/S0009-9120(02)00312-0] [PMID:  12135696]

[205]
Khorana AA, Ahrendt SA, Ryan CK, et al. Tissue factor expression, angiogenesis, and thrombosis in pancreatic cancer. Clin Cancer Res  2007; 13(10): 2870-5.
 [http://dx.doi.org/10.1158/1078-0432.CCR-06-2351] [PMID:  17504985]

[206]
Bluff JE, Menakuru SR, Cross SS, et al. Angiogenesis is associated with the onset of hyperplasia in human ductal breast disease. Br J Cancer  2009; 101(4): 666-72.
 [http://dx.doi.org/10.1038/sj.bjc.6605196] [PMID:  19623180]

[207]
Ueno T, Toi M, Koike M, Nakamura S, Tominaga T. Tissue factor expression in breast cancer tissues: its correlation with prognosis and plasma concentration. Br J Cancer  2000; 83(2): 164-70.
 [http://dx.doi.org/10.1054/bjoc.2000.1272] [PMID:  10901365]

[208]
de Heer EC, Jalving M, Harris AL. HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer. J Clin Invest  2020; 130(10): 5074-87.
 [http://dx.doi.org/10.1172/JCI137552] [PMID:  32870818]

[209]
Aalders KC, Tryfonidis K, Senkus E, Cardoso F. Anti-angiogenic treatment in breast cancer: Facts, successes, failures and future perspectives. Cancer Treat Rev  2017; 53: 98-110.
 [http://dx.doi.org/10.1016/j.ctrv.2016.12.009] [PMID:  28088074]

[210]
Bielenberg DR, Zetter BR. The contribution of angiogenesis to the process of metastasis. Cancer J  2015; 21(4): 267-73.
 [http://dx.doi.org/10.1097/PPO.0000000000000138] [PMID:  26222078]

[211]
Leppert U, Eisenreich A. The role of tissue factor isoforms in cancer biology. Int J Cancer  2015; 137(3): 497-503.
 [http://dx.doi.org/10.1002/ijc.28959] [PMID:  24806794]

[212]
Hobbs JE, Zakarija A, Cundiff DL, et al. Alternatively spliced human tissue factor promotes tumor growth and angiogenesis in a pancreatic cancer tumor model. Thromb Res  2007; 120(2): S13-21.
 [http://dx.doi.org/10.1016/S0049-3848(07)70126-3] [PMID:  18023707]

[213]
Chand HS, Ness SA, Kisiel W. Identification of a novel human tissue factor splice variant that is upregulated in tumor cells. Int J Cancer  2006; 118(7): 1713-20.
 [http://dx.doi.org/10.1002/ijc.21550] [PMID:  16217771]

[214]
Haas SL, Jesnowski R, Steiner M, et al. Expression of tissue factor in pancreatic adenocarcinoma is associated with activation of coagulation. World J Gastroenterol  2006; 12(30): 4843-9.
 [PMID:  16937466]

[215]
Pourgholami MH, Morris DL. Inhibitors of vascular endothelial growth factor in cancer. Cardiovasc Hematol Agents Med Chem  2008; 6(4): 343-7.
 [http://dx.doi.org/10.2174/187152508785909528]

[216]
Rousseau S, Houle F, Huot J. Integrating the VEGF signals leading to actin-based motility in vascular endothelial cells. Trends Cardiovasc Med  2000; 10(8): 321-7.
 [http://dx.doi.org/10.1016/S1050-1738(01)00072-X] [PMID:  11369257]

[217]
Issbrücker K, Martin HH, Hippenstiel S, et al. p38 MAP Kinase—a molecular switch between VEGF-induced angiogenesis and vascular hyperpermeability. FASEB J  2003; 17(2): 262-4.
 [http://dx.doi.org/10.1096/fj.02-0329fje] [PMID:  12490545]

[218]
Srinivasan R, Ozhegov E, Van Den Berg YW, et al. Splice variants of tissue factor promote monocyte endothelial interactions by triggering the expression of cell adhesion molecules via integrinš-mediated signaling. J Thromb Haemost  2011; 9(10): 2087-96.
 [http://dx.doi.org/10.1111/j.1538-7836.2011.04454.x] [PMID:  21812913]

[219]
Griffin CT, Srinivasan Y, Zheng YW, Huang W, Coughlin SR. A role for thrombin receptor signaling in endothelial cells during embryonic development. Science  2001; 293(5535): 1666-70.
 [http://dx.doi.org/10.1126/science.1061259] [PMID:  11533492]

[220]
Hadjipanayi E, Kuhn PH, Moog P, et al. The fibrin matrix regulates angiogenic responses within the hemostatic microenvironment through biochemical control. PLoS One  2015; 10(8): e0135618.
 [http://dx.doi.org/10.1371/journal.pone.0135618] [PMID:  26317771]

[221]
Amelot AA, Tagzirt M, Ducouret G, Kuen RL, Le Bonniec BF. Platelet factor 4 (CXCL4) seals blood clots by altering the structure of fibrin. J Biol Chem  2007; 282(1): 710-20.
 [http://dx.doi.org/10.1074/jbc.M606650200] [PMID:  17090548]

[222]
Barkefors I, Le Jan S, Jakobsson L, et al. Endothelial cell migration in stable gradients of vascular endothelial growth factor A and fibroblast growth factor 2: Effects on chemotaxis and chemokinesis. J Biol Chem  2008; 283(20): 13905-12.
 [http://dx.doi.org/10.1074/jbc.M704917200] [PMID:  18347025]

[223]
Ahmadi SE, Shabannezhad A, Kahrizi A, et al. Tissue factor (coagulation factor III): A potential double-edge molecule to be targeted and re-targeted toward cancer. Biomark Res  2023; 11(1): 60.
 [http://dx.doi.org/10.1186/s40364-023-00504-6] [PMID:  37280670]

[224]
Versteeg HH, Hoedemaeker I, Diks SH, et al. Factor VIIa/tissue factor-induced signaling via activation of Src-like kinases, phosphatidylinositol 3-kinase, and Rac. J Biol Chem  2000; 275(37): 28750-6.
 [http://dx.doi.org/10.1074/jbc.M907635199] [PMID:  10844001]

[225]
Jiao J, Kelly A, Marzec U, et al. Inhibition of acute vascular thrombosis in chimpanzees by an anti-human tissue factor antibody targeting the factor X binding site. Thromb Haemost  2010; 103(1): 224-33.
 [http://dx.doi.org/10.1160/TH09-06-0400] [PMID:  20062929]

[226]
Morris PE, Steingrub JS, Huang BY, et al. A phase I study evaluating the pharmacokinetics, safety and tolerability of an antibody-based tissue factor antagonist in subjects with acute lung injury or acute respiratory distress syndrome. BMC Pulm Med  2012; 12(1): 5.
 [http://dx.doi.org/10.1186/1471-2466-12-5] [PMID:  22340260]

[227]
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   2013; 110(28): 11517-22.
 [http://dx.doi.org/10.1073/pnas.1307100110] [PMID:  23801760]

[228]
Unruh D, Ünlü B, Lewis CS, et al. Antibody-based targeting of alternatively spliced tissue factor: a new approach to impede the primary growth and spread of pancreatic ductal adenocarcinoma. Oncotarget  2016; 7(18): 25264-75.
 [http://dx.doi.org/10.18632/oncotarget.7955] [PMID:  26967388]

[229]
Lewis CS, Karve A, Matiash K, et al. A first-in-class, humanized antibody targeting alternatively spliced tissue factor: Preclinical evaluation in an orthotopic model of pancreatic ductal adenocarcinoma. Front Oncol  2021; 11: 691685.
 [http://dx.doi.org/10.3389/fonc.2021.691685] [PMID:  34395257]

[230]
Lee SCW, Abdel-Wahab O. Therapeutic targeting of splicing in cancer. Nat Med  2016; 22(9): 976-86.
 [http://dx.doi.org/10.1038/nm.4165] [PMID:  27603132]
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DOI https://dx.doi.org/10.2174/0115665240258746230919165935	Print ISSN 1566-5240
Publisher Name Bentham Science Publisher	Online ISSN 1875-5666
Current Molecular Medicine

The Role of Tissue Factor In Signaling Pathways of Pathological Conditions and Angiogenesis

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