The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
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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Cites
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An Essential Role for Ectodomain Shedding in Mammalian Development
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Status of Epidermal Growth Factor Receptor Antagonists in the Biology and Treatment of Cancer
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Proteinase-activated Receptors
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Regulation of tyrosine kinase cascades by G-protein-coupled receptors
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Bhola, N. E. (2009) · D-Scholarship@Pitt (University of Pittsburgh)
THE ROLE OF TYROSINE PHOSPHORYLATION IN THE FUNCTIONS OF THE TUMOR SUPPRESSOR GPRC5A
Lin, X. (2010) · Digital Commons-TMC (Texas Medical Center)
Wadhwani, A. (2013) · Libraries and Cultural Resources (University of Calgary) · doi:10.11575/prism/26622
Shukla, A. K. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.736984636.793568776
Liu, Y., & Zhou, J. (2024) · British Journal of Hospital Medicine · doi:10.12968/hmed.2024.0220
Iyshwarya, B. K., Veerabathiran, R., Sivamani, G., & Nithyakalyani, M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-30098-1.00012-4
Additional file 1 of Diversification of PAR signaling through receptor crosstalk
Lee-Rivera, I., Edith, L., & López-Colomé, A. M. (2022) · Figshare · doi:10.6084/m9.figshare.21077871
Rôle de l'adrénomédulline dans le Mésothéliome pleural malin et le cancer bronchopulmonaire
Tounsi, A. (2014) · theses.fr (ABES) · doi:10.70675/b9b82f0az4fa4z4e5czbea5z12e3b53ee430
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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