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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.
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“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]
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EGF receptor activation by GPCRs: An universal pathway reveals different versions
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Protease-activated receptor-1 (PAR-1): a promising molecular target for cancer
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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 101
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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
Regulation of Src Family Kinases during Colorectal Cancer Development and Its Clinical Implications
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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
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“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.”
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Protease-activated receptors in cancer: A systematic review
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Huang, C., Chen, S., Tsai, H., Hsu, H., & Tang, C. (2012) · Arthritis & Rheumatism · doi:10.1002/art.34557 · Cited by 57
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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
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 56
“…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
“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.”
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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
“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
“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
“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) · The FEBS Journal · doi:10.1111/febs.15055 · Cited by 39
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“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
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Orexins/hypocretins and orexin receptors in apoptosis: a mini‐review
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“…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).”
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“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
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“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
“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).”
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“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 38
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“[25].”
Proteinase-activated receptors (PARs) in infection and inflammation in the gut
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Proteinases as hormones: targets and mechanisms for proteolytic signaling
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“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).”
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“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
“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
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
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
“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
“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
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
“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 23
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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
“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
“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
“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
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
Du, Z., Kim, K. H., Kim, J., & Moon, Y. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00186 · Cited by 14
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
“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
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 14
“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
“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
“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
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
“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
Lim, S., Kee, K.-H., Lee, M., Hong, R., & Han, S. I. (2020) · Oncology Reports · doi:10.3892/or.2020.7529 · Cited by 10
Heo, J. S., Lee, S. H., & Han, H. J. (2008) · Growth Factors · doi:10.1080/08977190802066655 · Cited by 9
“[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
“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
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
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
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
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
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
“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
“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
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
Tumor Tropism of Mesenchymal Stem Cells
Lam, P. Y. P., & Ho, I. A. W. (2013) · doi:10.1002/9781118660423.ch3 · Cited by 4
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
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
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
“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
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
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
Carcinogenèse colique, données fondamentales
Aparicio, T. (2007) · EMC - Gastro-entérologie · doi:10.1016/s1155-1968(07)43140-6 · Cited by 1
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
“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
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
Metadata
- 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
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