Activation of Proteinase-Activated Receptor 1 Promotes Human Colon Cancer Cell Proliferation Through Epidermal Growth Factor Receptor Transactivation
Open accessAbstract
Serine proteases are now considered as crucial contributors to the development of human colon cancer. We have shown recently that thrombin is a potent growth factor for colon cancer cells through activation of the aberrantly expressed protease-activated receptor 1 (PAR1). Here, we analyzed the signaling pathways downstream of PAR1 activation, which lead to colon cancer cell proliferation in HT-29 cells. Our data are consistent with the following cascade of events on activation of PAR1 by thrombin or specific activating peptide: (a) a matrix metalloproteinase–dependent release of transforming growth factor-α (TGF-α) as shown with TGF-α blocking antibodies and measurement of TGF-α in culture medium; (b) TGF-α-mediated activation of epidermal growth factor receptor (EGFR) and subsequent EGFR phosphorylation; and (c) activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) and subsequent cell proliferation. The links between these events are shown by the fact that stimulation of cell proliferation and ERK1/2 on activation of PAR1 is reversed by the MMP inhibitor batimastat, TGF-α neutralizing antibodies, EGFR ligand binding domain blocking antibodies, and the EGFR tyrosine kinase inhibitors AG1478 and PD168393. Therefore, transactivation of EGFR seems to be a major mechanism whereby activation of PAR1 results in colon cancer cell growth. Finally, PAR1 activation induces Src phosphorylation, which is reversed by using the Src tyrosine kinase inhibitor PP2, suggesting that Src activation plays a permissive role for PAR1-mediated ERK1/2 activation and cell proliferation probably acting downstream of the EGFR. These data explain how thrombin exerts robust trophic action on colon cancer cells and underline the critical role of EGFR transactivation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PARs have been implicated in the pathogenesis of colorectal cancer and inflammatory and functional intestinal disorders.
“PARs have been implicated in the pathogenesis of colorectal cancer138 and inflammatory and functional intestinal disorders.139–141”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [138]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
International Union of Pharmacology: Approaches to the Nomenclature of Voltage-Gated Ion Channels
Catterall, W. A., Chandy, K. G., Clapham, D. E., Gutman, G. A., Hofmann, F., Harmar, A. J., Abernethy, D. R., & Spedding, M. (2003) · Pharmacological Reviews · doi:10.1124/pr.55.4.5 · Cited by 7,126 · see citing works
Vu, T.-K. H., Hung, D. T., Wheaton, V. I., & Coughlin, S. R. (1991) · Cell · doi:10.1016/0092-8674(91)90261-v · Cited by 2,967 · see citing works
An Essential Role for Ectodomain Shedding in Mammalian Development
Peschon, J. J., Slack, J. L., Reddy, P., Stocking, K. L., Sunnarborg, S. W., Lee, D. C., Russell, W. E., Castner, B. J., Johnson, R. S., Fitzner, J. N., et al. (1998) · Science · doi:10.1126/science.282.5392.1281 · Cited by 1,606 · see citing works
Prenzel, N., Zwick, E., Daub, H., Leserer, M., Abraham, R., Wallasch, C., & Ullrich, A. (1999) · Nature · doi:10.1038/47260 · Cited by 1,507 · see citing works
Status of Epidermal Growth Factor Receptor Antagonists in the Biology and Treatment of Cancer
Mendelsohn, J. M., & Baselga, J. M. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.01.504 · Cited by 1,257 · see citing works
Proteinase-activated Receptors
Macfarlane, S. R., Seatter, M. J., Kanke, T., Hunter, G. D., & Plevin, R. J. (2006) · Springer eBooks · doi:10.1007/3-540-29832-0_1335 · Cited by 1,137 · see citing works
Pai, R., Soreghan, B. A., Szabó, I., Pavelka, M., Baatar, D., & Tarnawski, A. S. (2002) · Nature Medicine · doi:10.1038/nm0302-289 · Cited by 836 · see citing works
Harris, R. C. (2003) · Experimental Cell Research · doi:10.1016/s0014-4827(02)00105-2 · Cited by 786 · see citing works
Proteinase-activated receptors: novel mechanisms of signaling by serine proteases
Déry, O., Corvera, C. U., Steinhoff, M. S., & Bunnett, N. W. (1998) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1998.274.6.c1429 · Cited by 778 · see citing works
Regulation of tyrosine kinase cascades by G-protein-coupled receptors
Luttrell, L. M., Daaka, Y., & Lefkowitz, R. J. (1999) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(99)80023-4 · Cited by 688 · see citing works
Prenzel, N., Fischer, O. M., Streit, S., Hart, S., & Ullrich, A. (2001) · Endocrine Related Cancer · doi:10.1677/erc.0.0080011 · Cited by 673 · see citing works
Signal characteristics of G protein‐transactivated EGF receptor
Daub, H., Wallasch, C., Lankenau, A., Herrlich, A., & Ullrich, A. (1997) · The EMBO Journal · doi:10.1093/emboj/16.23.7032 · Cited by 647 · see citing works
Luttrell, L. M., Hawes, B. E., van Biesen, T., Luttrell, D. K., Lansing, T. J., & Lefkowitz, R. J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.32.19443 · Cited by 525 · see citing works
Trousseau, A. (1865) · Medical Entomology and Zoology · Cited by 502 · see citing works
Gβγ Subunits Mediate Src-dependent Phosphorylation of the Epidermal Growth Factor Receptor
Luttrell, L. M., Rocca, G. J. D., van Biesen, T., Luttrell, D. K., & Lefkowitz, R. J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.7.4637 · Cited by 457 · see citing works
International Union of Pharmacology. XXVIII. Proteinase-Activated Receptors
Hollenberg, M. D., & Compton, S. J. (2002) · Pharmacological Reviews · doi:10.1124/pr.54.2.203 · Cited by 441 · see citing works
Fry, D. W., Bridges, A. J., Denny, W. A., Doherty, A. M., Greis, K. D., Hicks, J. L., Hook, K. E., Keller, P. R., Leopold, W. R., Loo, J. A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.20.12022 · Cited by 424 · see citing works
Thrombin receptor overexpression in malignant and physiological invasion processes
Even‐Ram, S., Uziely, B., Cohen, P., Grisaru‐Granovsky, S., Maoz, M., Ginzburg, Y., Reich, R., Vlodavsky, I., & Bar‐Shavit, R. (1998) · Nature Medicine · doi:10.1038/nm0898-909 · Cited by 419 · see citing works
Sunnarborg, S. W., Hinkle, C. L., Stevenson, M. C., Russell, W. E., Raska, C. S., Peschon, J. J., Castner, B. J., GERHART, M. J., Paxton, R. J., Black, R. A., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m112050200 · Cited by 413 · see citing works
Maudsley, S. R., Pierce, K. L., Zamah, A. M., Miller, W. E., Ahn, S., Daaka, Y., Lefkowitz, R. J., & Luttrell, L. M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.13.9572 · Cited by 408 · see citing works
New mechanisms in heptahelical receptor signaling to mitogen activated protein kinase cascades
Pierce, K. L., Luttrell, L. M., & Lefkowitz, R. J. (2001) · Oncogene · doi:10.1038/sj.onc.1204184 · Cited by 393 · see citing works
Tissue Factor, Thrombin, and Cancer
Rickles, F. R., Patierno, S. R., & Fernández, P. M. (2003) · CHEST Journal · doi:10.1378/chest.124.3_suppl.58s · Cited by 378 · see citing works
TACE cleavage of proamphiregulin regulates GPCR‐induced proliferation and motility of cancer cells
Gschwind, A., Hart, S., Fischer, O. M., & Ullrich, A. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg231 · Cited by 344 · see citing works
Epidermal growth factor-related peptides and their relevance to gastrointestinal pathophysiology
Barnard, J. A., Beauchamp, R. D., Russell, W. E., DuBois, R. N., & Coffey, R. J. (1995) · Gastroenterology · doi:10.1016/0016-5085(95)90087-x · Cited by 326 · see citing works
Activation of MAPKs by Angiotensin II in Vascular Smooth Muscle Cells
Eguchi, S., Dempsey, P. J., Frank, G. D., Motley, E. D., & Inagami, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008570200 · Cited by 278 · see citing works
TACE is required for the activation of the EGFR by TGF‐α in tumors
Borrell-Pagés, M., Rojo, F., Albanell, J., Baselga, J., & Arribas, J. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg111 · Cited by 275 · see citing works
Roberts, R. B., Lu, M., Washington, M. K., Olsen, S. J., Settle, S. H., Coffey, R. J., & Threadgill, D. W. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.032678499 · Cited by 275 · see citing works
Employment of the Epidermal Growth Factor Receptor in Growth Factor–Independent Signaling Pathways
Carpenter, G. F. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.146.4.697 · Cited by 272 · see citing works
Differential expression of epidermal growth factor-related proteins in human colorectal tumors.
Ciardiello, F., Kim, N., Saeki, T., Dono, R., Persico, M. G., Plowman, G. D., Garrigues, J., Radke, S., Todaro, G. J., & Salomon, D. S. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.17.7792 · Cited by 267 · see citing works
Dong, J., Opresko, L. K., Dempsey, P. J., Lauffenburger, D. A., Coffey, R. J., & Wiley, H. S. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.11.6235 · Cited by 263 · see citing works
Epidermal Growth Factor (EGF) Receptor-dependent ERK Activation by G Protein-coupled Receptors
Pierce, K. L., Tohgo, A., Ahn, S., Field, M. E., Luttrell, L. M., & Lefkowitz, R. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101303200 · Cited by 215 · see citing works
Traxler, P. M., Bold, G., Frei, J., Lang, M., Lydon, N., Mett, H., Buchdunger, E., Meyer, T., Mueller, M., & Furet, P. (1997) · Journal of Medicinal Chemistry · doi:10.1021/jm970124v · Cited by 203 · see citing works
Extrinsic-pathway activation in cancer with high factor Vlla and tissue factor
Kakkar, A. K., DeRuvo, N., Chinswangwatanakul, V., Tebbutt, S. J., & Williamson, R. C. (1995) · The Lancet · doi:10.1016/s0140-6736(95)91690-3 · Cited by 199 · see citing works
Darmoul, D., Gratio, V., Devaud, H., Lehy, T., & Laburthe, M. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64283-6 · Cited by 193 · see citing works
Self-citationKalmes, A., Vesti, B. R., Daum, G., Abraham, J. A., & Clowes, A. W. (2000) · Circulation Research · doi:10.1161/01.res.87.2.92 · Cited by 182 · see citing works
Darmoul, D., Marie, J., Devaud, H., Gratio, V., & Laburthe, M. (2001) · British Journal of Cancer · doi:10.1054/bjoc.2001.1976 · Cited by 149 · see citing works
Self-citationKeely, S. J., Calandrella, S. O., & Barrett, K. E. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.17.12619 · Cited by 145 · see citing works
Johnson, G. R., Kannan, B., SHOYAB, M., & Stromberg, K. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53862-x · Cited by 138 · see citing works
Signaling from protease-activated receptor-1 inhibits migration and invasion of breast cancer cells.
Kamath, L., Meydani, A., Foss, F. M., & Kuliopulos, A. (2001) · PubMed · Cited by 136 · see citing works
Merlos‐Suárez, A., Ruíz-Paz, S., Baselga, J. M., & Arribas, J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103488200 · Cited by 132 · see citing works
Role of thrombin receptor in breast cancer invasiveness
Henrikson, K. P., Salazar, S. L., Fenton, J. W., & Pentecost, B. T. (1999) · British Journal of Cancer · doi:10.1038/sj.bjc.6690063 · Cited by 115 · see citing works
McCole, D. F., Keely, S. J., Coffey, R. J., & Barrett, K. E. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206487200 · Cited by 113 · see citing works
Cheng, K., Zimniak, P., & Raufman, J. (2003) · PubMed · Cited by 112 · see citing works
Sabri, A., Short, J., Guo, J., & Steinberg, S. F. (2002) · Circulation Research · doi:10.1161/01.res.0000035242.96310.45 · Cited by 107 · see citing works
Pearlstein, E., Ambrogio, C., Gasic, G., & Karpatkin, S. (1981) · PubMed · Cited by 96 · see citing works
Intracellular maturation and transport of tumor necrosis factor alpha converting enzyme
Peiretti, F., Canault, M., Deprez, P., Berthet, V., Bonardo, B., Juhan-Vague, I., & Nalbone, G. (2003) · Experimental Cell Research · doi:10.1016/s0014-4827(03)00052-1 · Cited by 81 · see citing works
Self-citationMechanisms of Protease-activated Receptor-4 Actions in Cardiomyocytes
Sabri, A., Guo, J., Elouardighi, H., Darrow, A. L., Andrade‐Gordon, P., & Steinberg, S. F. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m213091200 · Cited by 79 · see citing works
Epidermal growth factor receptor-targeted therapy in colorectal cancer
O'Dwyer, P. J., & BENSONIII, A. (2002) · Seminars in Oncology · doi:10.1016/s0093-7754(02)70086-9 · Cited by 72 · see citing works
Blobel, C. (2002) · Inflammation Research · doi:10.1007/bf02684007 · Cited by 66 · see citing works
Multiple Metalloproteinases Process Protransforming Growth Factor-α (ProTGF-α)
Hinkle, C. L., Mohan, M. J., Lin, P., Yeung, N., Rasmussen, F., Milla, M. E., & Moss, M. L. (2003) · Biochemistry · doi:10.1021/bi026709v · Cited by 53 · see citing works
Iversen, L. H., Okholm, M., & Thorlacius‐Ussing, O. (1996) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1650616 · Cited by 50 · see citing works
Rudroff, C., Seibold, S., Kaufmann, R., Zetina, C. C., Reise, K., Schäfer, U., Schneider, A., Brockmann, M. J., Scheele, J., & Neugebauer, E. A. M. (2002) · Clinical & Experimental Metastasis · doi:10.1023/a:1014598904644 · Cited by 41 · see citing works
Chiang, H., Swaim, M. W., & Huang, T. (1994) · British Journal of Haematology · doi:10.1111/j.1365-2141.1994.tb04917.x · Cited by 33 · see citing works
Ahrens, F., Gäbel, G., Garz, B., & Aschenbach, J. R. (2002) · Inflammation Research · doi:10.1007/pl00000275 · Cited by 32 · see citing works
Kaufmann, R., JUNKER, U., Nuske, K., Westermann, M., Henklein, P., Scheele, J., & Junker, K. (2002) · International Journal of Oncology · doi:10.3892/ijo.20.1.177 · Cited by 25 · see citing works
Expression of functional protease-activated receptor 1 in human prostate cancer cell lines
Liu, J., Bastian, M., Kohlschein, P., Schuff‐Werner, P., & Steiner, M. (2003) · Urological Research · doi:10.1007/s00240-003-0309-2 · Cited by 24 · see citing works
Modrau, I. S., Iversen, L. H., & Thorlacius‐Ussing, O. (2001) · Thrombosis Research · doi:10.1016/s0049-3848(01)00373-5 · Cited by 19 · see citing works
Cheng, K., Zimniak, P., & Raufman, J. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)82366-1 · Cited by 18 · see citing works
Garciá‐Avello, A., Galindo, J., Martínez-Molina, E., Cesar-Perez, J., & Navarro, J. L. (2001) · Thrombosis Research · doi:10.1016/s0049-3848(01)00383-8 · Cited by 16 · see citing works
Flagged first, then by citations
1 of the 60 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Structure, function and pathophysiology of protease activated receptors
Adams, M. N., Ramachandran, R., Yau, M.-K., Suen, J. Y., Fairlie, D. P., Hollenberg, M. D., & Hooper, J. D. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.01.003 · Cited by 370 · see citing works
Mechanisms for oncogenic activation of the epidermal growth factor receptor
Zandi, R., Larsen, A. B., Andersen, P., Stockhausen, M., & Poulsen, H. S. (2007) · Cellular Signalling · doi:10.1016/j.cellsig.2007.06.023 · Cited by 303 · see citing works
Protease inhibition as new therapeutic strategy for GI diseases
Vergnolle, N. (2016) · Gut · doi:10.1136/gutjnl-2015-309147 · Cited by 226 · see citing works
Dreux, A. C., Lamb, D. J., Modjtahedi, H., & Ferns, G. A. (2005) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2005.06.038 · Cited by 183 · see citing works
Gieseler, F., Ungefroren, H., Settmacher, U., Hollenberg, M. D., & Kaufmann, R. (2013) · Cell Communication and Signaling · doi:10.1186/1478-811x-11-86 · Cited by 180 · see citing works
“EGFR transactivation by PAR1 or PAR2 leading to COX2 expression [124], enhanced cell proliferation in colon carcinoma cells [112,113] and cell migration in renal”
BackgroundInfluentialCrosstalk between G-protein-coupled receptors and Epidermal growth factor receptor in cancer
Neil, E. B. (2007) · Frontiers in bioscience · doi:10.2741/2805 · Cited by 158 · see citing works
EGF receptor activation by GPCRs: An universal pathway reveals different versions
Liebmann, C. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.04.008 · Cited by 143 · see citing works
Arora, P., Cuevas, B. D., Russo, A., Johnson, G. L., & Trejo, J. (2008) · Oncogene · doi:10.1038/onc.2008.84 · Cited by 124 · see citing works
“Previous studies have shown that several GPCR agonists including thrombin are capable of inducing transactivation of EGFR in both transformed and nontransformed cells (Daub et al., 1996; Prenzel et al., 1999; Darmoul et al., 2004; Bergman et al., 2006).”
BackgroundColon Cancer Growth and Dissemination Relies upon Thrombin, Stromal PAR-1, and Fibrinogen
Adams, G. N., Rosenfeldt, L. A., Frederick, M. D., Miller, W., Waltz, D., Kombrinck, K. W., McElhinney, K. E., Flick, M. J., Monia, B. P., Revenko, A. S., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-15-0964 · Cited by 123 · see citing works
“Previous in vitro studies suggested that activation of tumor cell–associated PAR-1 promotes colon cancer proliferation and invasion (42, 43).”
Protease-activated receptor-1 (PAR-1): a promising molecular target for cancer
Liu, X., Yu, J., Song, S., Yue, X., & Li, Q. (2017) · Oncotarget · doi:10.18632/oncotarget.21015 · Cited by 102 · see citing works
“PAR-1 signaling enhances cancer cell invasion via Rho-Rho kinase axis and tumor microenvironment [89].”
BackgroundGastrointestinal roles for proteinase‐activated receptors in health and disease
Kawabata, A., Matsunami, M., & Sekiguchi, F. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707491 · Cited by 98 · see citing works
“Apart from cancer cell lines (Darmoul et al., 2004a, b; Nguyen et al., 2005), cellular signalling triggered by activation of PARs in normal GI epithelial cells has not been well understood.”
BackgroundGPR54 (KISS1R) Transactivates EGFR to Promote Breast Cancer Cell Invasiveness
Zajac, M., Law, J., Cvetkovic, D. D., Pampillo, M., McColl, L., Pape, C., Guglielmo, G. M. D., Postovit, L.-M. M., Babwah, A. V., & Bhattacharya, M. M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021599 · Cited by 97 · see citing works
“EGFR can be transactivated by GPCRs in a variety of cell types including tumor cells [15,16,17,18].”
BackgroundThe emerging roles of bacterial proteases in intestinal diseases
Caminero, A., Guzman, M., Libertucci, J., & Lomax, A. E. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2181922 · Cited by 92 · see citing works
Regulation of Src Family Kinases during Colorectal Cancer Development and Its Clinical Implications
Jin, W. (2020) · Cancers · doi:10.3390/cancers12051339 · Cited by 86 · see citing works
“Additionally, Src-mediated ERK1/2 activation suppresses apoptosis of CRC cells through ubiquitin-mediated degradation of Bik, a death accelerator [57].”
BackgroundInfluentialThrombin Signaling Promotes Pancreatic Adenocarcinoma through PAR-1–Dependent Immune Evasion
Yang, Y., Stang, A., Schweickert, P. G., Lanman, N. A., Paul, E. N., Monia, B. P., Revenko, A. S., Palumbo, J. S., Mullins, E. S., Elzey, B. D., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-3206 · Cited by 84 · see citing works
(2019) · doi:10.1371/journal.pbio.3000434 · Cited by 79 · see citing works
“Evidence for functional roles in cancer cells of GPCRs that are highly expressed and overexpressed in solid tumors and cancer cells include findings for PAR1/F2R in BRCA [25], gastric cancer [26], colon cancer [27], and melanoma [28] cells and for PAR2/F2RL1 in melanoma [28], BRCA [29], and colon cancer cells [30].”
BackgroundSokolova, E., & Reiser, G. (2007) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2007.04.002 · Cited by 65 · see citing works
Hsieh, H., Sun, C., Wang, T.-S., & Yang, C. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2008.03.016 · Cited by 65 · see citing works
Voisin, T., Firar, A. E., Rouyer‐Fessard, C., Gratio, V., & Laburthe, M. (2008) · The FASEB Journal · doi:10.1096/fj.07-098723 · Cited by 65 · see citing works
“Indeed, a variety of GPCRs in colon cancer cells, such as NTS1 receptor for neurotensin (12), protease-activated receptors for thrombin or trypsin (13) or muscarinic M3 receptor for acetylcholine (14), are known to promote the increase of intracellular calcium.”
BackgroundSelf-citationGPCRs and EGFR – Cross-talk of membrane receptors in cancer
Köse, M. (2017) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2017.07.002 · Cited by 64 · see citing works
Protease-activated receptors in cancer: A systematic review
Han, N., Jin, K., He, K., Cao, J., & Teng, L. (2011) · Oncology Letters · doi:10.3892/ol.2011.291 · Cited by 59 · see citing works
“Thrombin markedly increases the growth potential of tumor cells (Table III) (74-81), although these effects may be partially attributed to its pro-angiogenic effects (27,82).”
Huang, C., Chen, S., Tsai, H., Hsu, H., & Tang, C. (2012) · Arthritis & Rheumatism · doi:10.1002/art.34557 · Cited by 57 · see citing works
Gao, L., Chao, L., & Chao, J. (2009) · Experimental Cell Research · doi:10.1016/j.yexcr.2009.10.022 · Cited by 57 · see citing works
“Transactivation of EGFR is related to activation of PAR1 in proliferation of human colon cancer cells, as well as of cardiac fibroblasts and cardiomyocytes [12,38].”
BackgroundKallikrein-Related Peptidase 4
Gratio, V., Beaufort, N., Seiz, L., Maier, J., Virca, G. D., Debela, M., Grebenchtchikov, N. I., Magdolen, V., & Darmoul, D. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.090523 · Cited by 54 · see citing works
Self-citationKallikrein 6 is a novel molecular trigger of reactive astrogliosis
Scarisbrick, I. A., Radulovic, M., Burda, J. E., Larson, N., Blaber, S. I., Giannini, C., Blaber, M., & Vandell, A. G. (2012) · Biological Chemistry · doi:10.1515/hsz-2011-0241 · Cited by 55 · see citing works
“…on the agonist, activation of PAR1 has also been associated with transactivation of the epidermal growth factor receptor (Prenzel et al. , 1999 ; Darmoul et al. , 2004 ; Arora et al. , 2008 ) and potentiation of N-methyl- D -aspartate receptor responses (Gingrich et al. , 2000 ; Hamill et al. ,…”
Al‐Ani, B., Hewett, P. W., Cudmore, M., Fujisawa, T., Saifeddine, M., Williams, H., Ramma, W., Sissaoui, S., Jayaraman, P.-S., Ohba, M., et al. (2010) · Hypertension · doi:10.1161/hypertensionaha.109.136333 · Cited by 49 · see citing works
“29,30,36 Inhibition of Src or EGFR completely abrogated PAR-2–mediated sVEGFR-1 expression, indicating that both Src and EGFR activation is required in concert with PKC for the efficient release of sVEGFR-1 in response to PAR-2.”
Chu, X., Filali, M. S., Stanić, B., Takapoo, M., Sheehan, A. L., Bhalla, R. C., Lamb, F. S., & Miller, F. J. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.217604 · Cited by 51 · see citing works
Gratio, V., Loriot, C., Virca, G. D., Οικονομοπούλου, Κ., Walker, F., Diamandis, E. P., Hollenberg, M. D., & Darmoul, D. (2011) · American Journal Of Pathology · doi:10.1016/j.ajpath.2011.07.016 · Cited by 50 · see citing works
Self-citationProtease-Activated Receptors in the Intestine: Focus on Inflammation and Cancer
Sébert, M., Tapias, N. S., Mas, E., Barreau, F., & Ferrand, A. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00717 · Cited by 48 · see citing works
“Since, it has been demonstrated that PAR1 plays a direct role in the progression of epithelial colon tumors, regulating both cell proliferation and migration (4, 121, 122) have pro- and anti-apoptotic effects, depending on the dose of thrombin or agonist peptides used (123).”
BackgroundGratio, V., Walker, F., Lehy, T., Laburthe, M., & Darmoul, D. (2008) · International Journal of Cancer · doi:10.1002/ijc.24070 · Cited by 47 · see citing works
“The expression of PAR1, the predominant thrombin receptor, has been associated with human colon carcinogenesis.(14,15) Since little is known in cancer about the role of PAR4, the latest thrombin receptor described, we addressed the issue of the expression and function of PAR4 in human colon cancer.”
BackgroundSelf-citationFujimoto, D., Hirono, Y., Goi, T., Katayama, K., Matsukawa, S., & Yamaguchi, A. (2010) · BMC Cancer · doi:10.1186/1471-2407-10-443 · Cited by 46 · see citing works
“Thus, although we also have shown that NF- B and EGFR activation initially were triggered by activation of PAR1 in the early phase (Figures 8 &13) [19,33] the sustained responses very likely are mediated by ‘feed-forward’ mechanisms, possibly involving the production of autocrine stimulatory factors like the one(s) de…”
BackgroundInfluentialProtease‐activated receptor signaling in intestinal permeability regulation
Pontarollo, G., Mann, A., Brandão, I., Malinarich, F., Schöpf, M., & Reinhardt, C. (2019) · FEBS Journal · doi:10.1111/febs.15055 · Cited by 48 · see citing works
Müller, K. M., Tveteraas, I. H., Aasrum, M., Ødegård, J., Dawood, M., Dajani, O. F., Christoffersen, T., & Sandnes, D. (2011) · BMC Cancer · doi:10.1186/1471-2407-11-421 · Cited by 45 · see citing works
“A plausible explanation is the autocrine production of TGFa and other ligands, leading to constitutive activation of EGFR in HCT116 cells [47-49].”
ResultInfluentialTF/FVIIa Transactivate PDGFRβ to Regulate PDGF-BB–Induced Chemotaxis in Different Cell Types
Siegbahn, A., Johnell, M., Nordin, A., Åberg, M., & Velling, T. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.155754 · Cited by 45 · see citing works
Vesey, D. A., Cheung, C. W. Y., Kruger, W. A., Poronnik, P., Gobe, G. C., & Johnson, D. W. (2005) · Kidney International · doi:10.1111/j.1523-1755.2005.00209.x · Cited by 44 · see citing works
Huang, C., Lin, H.-J., Chen, H.-S., Cheng, S., Hsu, H., & Tang, C. (2013) · Mediators of Inflammation · doi:10.1155/2013/326041 · Cited by 43 · see citing works
Orexins/hypocretins and orexin receptors in apoptosis: a mini‐review
Laburthe, M., Voisin, T., & Firar, A. E. (2009) · Acta Physiologica · doi:10.1111/j.1748-1716.2009.02035.x · Cited by 42 · see citing works
“…growth factors for colon cancer cells have been extensively described (Rozengurt et al. 2002) including agonists for tyrosine kinase receptors and for some G-protein-coupled receptors (GPCR) which often work through transactivation of the epidermal growth factor receptor (Darmoul et al. 2004a,b).”
BackgroundSelf-citationCouvineau, A., Dayot, S., Nicole, P., Gratio, V., Rebours, V., Couvelard, A., & Voisin, T. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00573 · Cited by 41 · see citing works
“The peptide hormones mediated-growth effects such as gastrin (34) or neurotensin (33), serine proteases such as thrombin (35) or trypsin (37) or lipids such as lysophosphatidic acid (38) or prostaglandin E2 (39) are promoted through GPCRs.”
Self-citationPAR2 induces ovarian cancer cell motility by merging three signalling pathways to transactivate EGFR
Jiang, Y., Lim, J., Wu, K., Xu, W., Suen, J. Y., & Fairlie, D. P. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15332 · Cited by 39 · see citing works
Fernández-Patrón, C. (2007) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y06-097 · Cited by 39 · see citing works
“Previous research on the transactivation pathway has focused primarily on the contribution of this mechanism to the development and progression of cancer (Pai et al. 2002; Darmoul et al. 2004; Shah and Catt 2004; Tanaka et al. 2004).”
BackgroundHo, I. A. W., Yulyana, Y., Sia, K. C., Newman, J. P. A., Guo, C. M., Hui, K. M., & Lam, P. Y. P. (2014) · The FASEB Journal · doi:10.1096/fj.14-252551 · Cited by 38 · see citing works
“Receptor transactivation can occur through different mechanisms; for example, activation of EGFR through direct interaction with PAR-1 led to migration of renal carcinoma (24) and colon cancer cells (25).”
BackgroundGao, L., SMITH, R. S., Chen, L., Chai, K. X., Chao, L., & Chao, J. (2010) · Biological Chemistry · doi:10.1515/bc.2010.084 · Cited by 38 · see citing works
Chang, L., Chen, C., Huang, D., Pai, H., Pan, S., & Teng, C. (2010) · Journal of Cellular Physiology · doi:10.1002/jcp.22428 · Cited by 38 · see citing works
“Upregulation of PAI-1 also associated with metastasis in hypoxic tumor microenvironments (Denko and Giaccia, 2001).”
BackgroundERBBs in the gastrointestinal tract: Recent progress and new perspectives
Fiske, W. H., Threadgill, D. W., & Coffey, R. J. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.10.043 · Cited by 37 · see citing works
Bergmann, S., Junker, K., Henklein, P., Hollenberg, M. D., Settmacher, U., & Kaufmann, R. (2006) · Oncology Reports · doi:10.3892/or.15.4.889 · Cited by 36 · see citing works
Buffin‐Meyer, B., Crassous, P., Delage, C., Denis, C., Schaak, S., & Paris, H. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.07.014 · Cited by 34 · see citing works
Chi, P., Luo, S., Hsieh, H., Lee, I.-T., Hsiao, L., Chen, Y., & Yang, C. (2011) · Arthritis & Rheumatism · doi:10.1002/art.30504 · Cited by 32 · see citing works
Yang, C., Hsiao, L., Yang, C., & Lin, C. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-9916-0 · Cited by 32 · see citing works
“[25].”
Proteinase-activated receptors (PARs) in infection and inflammation in the gut
Vergnolle, N. (2008) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2008.01.016 · Cited by 31 · see citing works
Proteinases as hormones: targets and mechanisms for proteolytic signaling
Hansen, K. K., Οικονομοπούλου, Κ., Baruch, A., Ramachandran, R., Beck, P. L., Diamandis, E. P., & Hollenberg, M. D. (2008) · Biological Chemistry · doi:10.1515/bc.2008.120 · Cited by 31 · see citing works
“This trans-activation of the EGF receptor can result from activating a variety of GPCRs, even including PAR1 (Darmoul et al., 2004; Bergmann et al., 2006).”
BackgroundHurtado, M., Lozano, J. J., Castellanos, E., López-Fernández, L. A., Harshman, K., Martínez‐A, C., Ortiz, A. R., Thomson, T. M., & Paciucci, R. (2007) · Gut · doi:10.1136/gut.2006.097188 · Cited by 31 · see citing works
Zecchin, D., Moore, C., Michailidis, F., Horswell, S. D., Rana, S., Howell, M. T., & Downward, J. (2020) · EMBO Molecular Medicine · doi:10.15252/emmm.202011987 · Cited by 29 · see citing works
McCole, D. F., Truong, A., Bunz, M., & Barrett, K. E. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700424200 · Cited by 29 · see citing works
Delaunay, T., Deschamps, L., Haddada, M., Walker, F., Soosaipillai, A. R., Soualmia, F., Amri, C. E., Diamandis, E. P., Brattsand, M., Magdolen, V., et al. (2017) · Molecular Oncology · doi:10.1002/1878-0261.12103 · Cited by 26 · see citing works
“Cells were lysed with RIPA buffer as described (Darmoul et al., 2004).”
BackgroundMethodSelf-citationChung, H., Hamza, M. M., Οικονομοπούλου, Κ., Gratio, V., Saifeddine, M., Virca, G. D., Diamandis, E. P., Hollenberg, M. D., & Darmoul, D. (2011) · Biological Chemistry · doi:10.1515/bc-2011-231 · Cited by 24 · see citing works
“As expected, PAR-2 siRNA had no effect on thrombin-induced ERK/MAP kinase phosphorylation mediated by PAR-1 (Darmoul et al. , 2004a ).”
InfluentialSelf-citationSekiguchi, F., Saito, S., Takaoka, K., Hayashi, H. D., Nagataki, M., Nagasawa, K., Nishikawa, H., Matsui, H., & Kawabata, A. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.09.016 · Cited by 24 · see citing works
Matrix metalloproteinase‐1 facilitates MSC migration via cleavage of IGF ‐2/ IGFBP 2 complex
Guan, S. P., Lam, A. T., Newman, J. P. A., Chua, K. L. M., Kok, C. Y. L., Chong, S. T., Chua, M. L. K., & Lam, P. Y. P. (2017) · FEBS Open Bio · doi:10.1002/2211-5463.12330 · Cited by 23 · see citing works
Bouzid, H., Soualmia, F., Οικονομοπούλου, Κ., Soosaipillai, A. R., Walker, F., Louati, K., Dico, R. L., Pocard, M. D., Amri, C. E., Ignatenko, N. A., et al. (2022) · Biomolecules · doi:10.3390/biom12071003 · Cited by 22 · see citing works
“By using immunofluorescence microscopy with antibodies directed against the N–terminal domains of either PAR1 or PAR2, we examined the loss of PAR1 and PAR2 immunoreactivity at the cell surface of KLK6-treated HT-29 cells.”
BackgroundMethodInfluentialSelf-citationBeidler, C. B., Petrovan, R. J., Conner, E. M., Boyles, J. S., Yang, D. D., Harlan, S. M., Chu, S., Ellis, B., Datta‐Mannan, A., Johnson, R. L., et al. (2014) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.210765 · Cited by 22 · see citing works
“Both thrombin and TNF-a have been shown to induce EGFR phosphorylation and ERK1/2 activation through EGFR transactivation (Darmoul et al., 2004; Ueno et al., 2005).”
BackgroundHuang, B., Chen, T.-S., BAU, D.-T., Chuang, I.-C., Tsai, C., Chang, P.-C., & Lu, D. (2017) · Scientific Reports · doi:10.1038/s41598-017-09122-3 · Cited by 22 · see citing works
Diversification of PAR signaling through receptor crosstalk
Lee-Rivera, I., López, E., & López-Colomé, A. M. (2022) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-022-00382-0 · Cited by 21 · see citing works
“On the other hand, as expected, the induction of COX-2 is delayed, and is mediated by ERK1/2, p38 MAPK, Src and EGF receptors (Fig.”
BackgroundInfluentialTargeting G protein-coupled receptors in cancer therapy
Soond, S. M., & Zamyatnin, A. A. (2019) · Advances in cancer research · doi:10.1016/bs.acr.2019.11.002 · Cited by 21 · see citing works
Ohshiro, K., Bui-Nguyen, T. M., Reddy, S. D. N., Schwartz, A. M., Levine, P. H., & Kumar, R. (2012) · The International Journal of Biological Markers · doi:10.5301/jbm.2012.10437 · Cited by 20 · see citing works
Proteinase-Activated Receptors (PARs) and Calcium Signaling in Cancer
Kaufmann, R., & Hollenberg, M. D. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-94-007-2888-2_45 · Cited by 20 · see citing works
“In cells from this tumour entity, PAR 1 and PAR 2 have been demonstrated to signal via [Ca 2+ ] i and to induce migratory and proliferative effects that also involve both activation of p42/p44-MAPKinase and trans-activation of the receptor for epidermal growth factor (EGFR) [ 64, 74, 88, 89 ] .”
BackgroundAnticoagulant therapy of cancer patients: Will patient selection increase overall survival?
Versteeg, H. H., Borensztajn, K., & Spek, C. A. (2015) · Thrombosis and Haemostasis · doi:10.1160/th15-02-0124 · Cited by 19 · see citing works
“Similarly, activation of PAR-1 enhances colon cancer cell proliferation (73) and renal cancer cell migration (74) through EGFR transactivation, whereas PAR-2 activation leads to transactivation of EGFR in gastric cancer cells thereby promoting proliferation (75).”
BackgroundProteinase-activated receptors (PARs) as targets for antiplatelet therapy
Cunningham, M., McIntosh, K., Bushell, T. J., Sloan, G., & Plevin, R. J. (2016) · Biochemical Society Transactions · doi:10.1042/bst20150282 · Cited by 19 · see citing works
“In addition to coupling to G proteins, PARs are known to signal via interaction with adapter proteins such as β-arrestin 1 and 2 [33] and transactivation of receptor kinases such as EGFR [34].”
BackgroundLu, T., Kuo, F., Lu, T., Hsu, C.-Y., & Fu, H. (2006) · Cellular Signalling · doi:10.1016/j.cellsig.2006.03.002 · Cited by 19 · see citing works
Role of Protease-Activated Receptor-1 in Glioma Growth
Xie, Q. M., Bao, X., Chen, Z. H., Xu, Y., Keep, R. F., Muraszko, K. M., Xi, G., & Hua, Y. (2016) · Acta neurochirurgica. Supplementum · doi:10.1007/978-3-319-18497-5_61 · Cited by 17 · see citing works
Du, Z., Kim, K. H., Kim, J., & Moon, Y. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00186 · Cited by 14 · see citing works
A Novel Compound Targeting Protease Receptor 1 Activators for the Treatment of Glioblastoma
Stein, E. S., Sheinberg, E., Golderman, V., Sharabi, S., Wohl, A., Gofrit, S. G., Zivli, Z., Shelestovich, N., Last, D., Guez, D., et al. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.01087 · Cited by 14 · see citing works
“Thrombin, via PAR1 activation, is known to act as a growth factor and proliferation inducer (16, 17).”
BackgroundProtease-Activated Receptors, Apoptosis and Tumor Growth
Borensztajn, K., & Spek, C. A. (2007) · Pathophysiology of Haemostasis and Thrombosis · doi:10.1159/000175152 · Cited by 14 · see citing works
Hajjo, R., Sabbah, D. A., Bardaweel, S. K., & Zhong, H. A. (2024) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2024.2327307 · Cited by 12 · see citing works
“Increased copy numbers by amplification, transactivation by different receptors, and enhanced expression of EGFR and its ligands are seen in many cancers [47–49].”
BackgroundSTAT3-mediated Coincidence Detection Regulates Noncanonical Immediate Early Gene Induction
Waitkus, M. S., Chandrasekharan, U. M., Willard, B. B., Haque, S. J., & DiCorleto, P. E. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.428516 · Cited by 13 · see citing works
“Crosstalk is an important factor in a number of biological processes, including cellular migration (5), proliferation (6), gene expression (7, 8), and calcium influx (4).”
BackgroundWang, T. (2012) · Oncology Reports · doi:10.3892/or.2012.1802 · Cited by 12 · see citing works
“PAR-1 activation is known to induce proliferation of endothelial cells (33) and a few tumor cell types (34,35).”
BackgroundZamel, I. A., Palakkott, A. R., Ashraf, A., Iratni, R., & Ayoub, M. A. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.01283 · Cited by 11 · see citing works
Jiang, P., Li, S. D., Li, Z. G., Zhu, Y., Yi, X. J., & Li, S. M. (2018) · Cancer Cell International · doi:10.1186/s12935-018-0577-0 · Cited by 11 · see citing works
“epidermal growth factor receptor activation to drive cell proliferation in human colon cancer cells [16], and is associated with increased bone metastases in prostate cancer cells [17].”
Walter, J., Handel, L. L., Brodhun, M., van Rossum, D., Hanisch, U., Liebmann, L., Heppner, F. L., Goldbrunner, R., Koch, A., & Kuhn, S. A. (2011) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-011-1078-x · Cited by 10 · see citing works
Lim, S., Kee, K.-H., Lee, M., Hong, R., & Han, S. I. (2020) · Oncology Reports · doi:10.3892/or.2020.7529 · Cited by 10 · see citing works
Heo, J. S., Lee, S. H., & Han, H. J. (2008) · Growth Factors · doi:10.1080/08977190802066655 · Cited by 9 · see citing works
“[14] Darmoul D, Gratio V, Devaud H, Peiretti F, Laburthe M.”
BackgroundGuignard, S., Saifeddine, M., Mihara, K., Motahhary, M., Savignac, M., Guiraud, L., Sagnat, D., Sebbag, M., Khou, S., Rolland, C., et al. (2024) · British Journal of Pharmacology · doi:10.1111/bph.16341 · Cited by 9 · see citing works
“The same group reported that activation of PAR1 by thrombin or its agonist peptide TFLLR drives proliferation of HT29 cells (Darmoul et al., 2004).”
BackgroundWang, W., Zhang, X., Mize, G. J., & Τakayama, T. K. (2008) · The Prostate · doi:10.1002/pros.20767 · Cited by 9 · see citing works
Proteases in intestinal health and disease
Deraison, C., & Vergnolle, N. (2025) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-025-01129-w · Cited by 9 · see citing works
Angiogenesis, haemostasis and cancer: new paradigms and old concerns
Duarte, M. F., Longatto‐Filho, A., & Schmitt, F. C. (2007) · Jornal Brasileiro de Patologia e Medicina Laboratorial · doi:10.1590/s1676-24442007000600009 · Cited by 7 · see citing works
Analyses of domains and domain fusions in human proto-oncogenes
Liu, Q., Huang, J., Liu, H., Wan, P., Ye, X., & Xu, Y. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-88 · Cited by 7 · see citing works
Photonanozyme–Kras–ribosome combination treatment of non-small cell lung cancer after COVID-19
Si, Q., Bai, M., Wang, X., Wang, T., & Qin, Y. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1420463 · Cited by 5 · see citing works
Protease-Activated Receptors (PARs): Biology and Therapeutic Potential in Perioperative Stroke
Mavridis, T., Choratta, T., Papadopoulou, A., Sawafta, A., Barakakis, P. A., Laou, E., Sakellakis, M., & Chalkias, A. F. (2024) · Translational Stroke Research · doi:10.1007/s12975-024-01233-0 · Cited by 5 · see citing works
“The activation of PAR-1 and PAR-2 leads to epidermal growth factor receptor (EGFR) transactivation, eliciting proliferative effects in various cancer types, including lung, colon, kidney, gastric cancer, and malignant melanoma [55–57].”
Coagulation proteases and neurotransmitters in pathogenicity of glioblastoma multiforme
Tripathy, S., Singh, S., Banerjee, M., Modi, D. R., & Prakash, A. (2022) · International Journal of Neuroscience · doi:10.1080/00207454.2022.2107514 · Cited by 5 · see citing works
“Through PAR1 activation, thrombin acts as a growth factor and proliferation inducer [ 25 , 26 ].”
BackgroundThrombin Receptor Modulators: Medicinal Chemistry, Biological Evaluation, and Clinical Application
Chen, C., Maryanoff, B. E., & Andrade‐Gordon, P. (2008) · Springer eBooks · doi:10.1007/978-0-387-09637-7_12 · Cited by 5 · see citing works
Tekin, C., Scicluna, B. P., Lodestijn, S. C., Shi, K., Bijlsma, M. F., & Spek, C. A. (2021) · Molecular Oncology · doi:10.1002/1878-0261.12971 · Cited by 4 · see citing works
Tumor Tropism of Mesenchymal Stem Cells
Lam, P. Y. P., & Ho, I. A. W. (2013) · doi:10.1002/9781118660423.ch3 · Cited by 4 · see citing works
PRASAIN, J. K., Arabshahi, A., Moore, R., Barnes, S., & Carroll, S. L. (2008) · Journal of Chromatography B · doi:10.1016/j.jchromb.2008.10.046 · Cited by 3 · see citing works
Protease-activated receptor 1 mediated altered Ca+2 signaling in gliomas
Tripathy, S., Almutairi, B. O., Singh, S., Rawat, A. K., Dubey, D., Banerjee, M., Modi, D. R., & Prakash, A. (2022) · Journal of King Saud University - Science · doi:10.1016/j.jksus.2022.102039 · Cited by 2 · see citing works
The Role of Coagulation Factor Signaling in Angiogenesis and Vascular Remodeling
Reinhardt, C., Manukyan, D., & Ruf, W. (2015) · Springer eBooks · doi:10.1007/978-1-4939-2907-8_10 · Cited by 2 · see citing works
“Expression and activation of PAR1 has been associated with tumor progression in prostate cancer, breast cancer, lung cancer, gastric cancer, colon cancer, melanoma, and ovarian cancer [163–170].”
BackgroundProteinases as hormones: targets and mechanisms for proteolytic signaling
Hansen, K. K., Οικονομοπούλου, Κ., Baruch, A., Ramachandran, R., Beck, P. L., Diamandis, E. P., & Hollenberg, M. D. (2008) · Biological Chemistry · doi:10.1515/bc.2008.120_bchm.just-accepted · Cited by 2 · see citing works
Kallikrein-Related Peptidase 5
Goettig, P., & Magdolen, V. (2012) · Handbook of Proteolytic Enzymes · doi:10.1016/b978-0-12-382219-2.00611-6 · Cited by 1 · see citing works
Endothelial protein C receptor: location…with a pool!
Weiler-Guettler, H. (2007) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2007.02599.x · Cited by 1 · see citing works
Carcinogenèse colique, données fondamentales
Aparicio, T. (2007) · EMC - Gastro-entérologie · doi:10.1016/s1155-1968(07)43140-6 · Cited by 1 · see citing works
Tumor cell apoptosis mediated by the orexins
Diatlova, A., Novikova, N. S., Derevtsova, K. Z., & Korneva, E. A. (2021) · Medical Immunology (Russia) · doi:10.15789/1563-0625-tca-2105 · Cited by 1 · see citing works
“Известно, что различные GPCRs, такие как рецептор NTS1 для нейротензина [31], активированные протеазой рецепторы тромбина или трипсина [12] или мускариновый рецептор M3 [18], способствуют повышению концентрации внутриклеточного кальция в клетках толстой кишки.”
KALLIKREIN-RELATED PEPTIDASE SIGNALLING VIA PROTEINASE-ACTIVATED RECEPTORS
Oikonomopoulou, A. (2008) · TSpace (University of Toronto) · Cited by 1 · see citing works
Role of Bile Acids in Carcinogenesis of Gastrointestinal Tract
Yasuda, H., & Itoh, F. (2011) · Springer eBooks · doi:10.1007/978-1-4614-0730-0_6
- Authors
- Darmoul, D., Gratio, V., Devaud, H., Peiretti, F., & Laburthe, M.
- Affiliations
- Inserm (FR)
- 1Neuroendocrinologie et Biologie Cellulaire Digestives, Institut National de la Sante et de la Recherche Medicale, Paris, France and
- Hôpital de la Timone (FR)
- Venue
- Molecular Cancer Research
- Published
- 2004-09-01
- Volume
- 2
- Issue
- 9
- Pages
- 514-522
- ISSN
- 1541-7786 (ISSN-L)
- 1557-3125
- OpenAlex
- W2181958706
- Cited by
- 109
- References
- 60
- Citations by year
- 2025: 1 · 2024: 6 · 2023: 1 · 2022: 5 · 2021: 2 · 2020: 5 · 2019: 6 · 2018: 4 · 2017: 6 · 2016: 4 · 2015: 3 · 2014: 3 · 2013: 5 · 2012: 6
- FWCI
- 2.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- protease-activated receptor 1, thrombin, colon cancer, EGFR transactivation, epidermal growth factor receptor, transforming growth factor-alpha, matrix metalloproteinases, ERK signaling, cell proliferation, Src kinase, serine protease, HT-29 cells, batimastat, EGFR tyrosine kinase inhibitors
- MeSH terms
- Antibodies, Monoclonal, Colonic Neoplasms, Enzyme Activation, Humans, Phosphorylation, Transcriptional Activation, Gene Expression Regulation, Neoplastic, Transforming Growth Factor alpha, src-Family Kinases, Matrix Metalloproteinases, Receptor, PAR-1, Cell Line, Tumor, Extracellular Signal-Regulated MAP Kinases, Cell Proliferation, Matrix Metalloproteinase Inhibitors, ErbB Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
