ArticleThe Journal of biological chemistry2009
Crosstalk between protease-activated receptor 1 and platelet-activating factor receptor regulates melanoma cell adhesion molecule (MCAM/MUC18) expression and melanoma metastasis.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
52 citing papers in PubMed, 75 citations in OpenAlex.
- Melanoma cell adhesion molecule (MCAM) mediates microtentacle generation, homotypic clustering, and reattachment of non-adherent breast tumor cells.Breast cancer research : BCR · 2026Article
- Platelet-activating factor and protease-activated receptor 2 cooperate to promote neutrophil recruitment and lung inflammation through nuclear factor-kappa B transactivation.Scientific reports · 2023Article
- CD146-targeted nuclear medicine imaging in cancer: state of the art.View (Beijing, China) · 2023Article
- PLA2G7/PAF-AH as Potential Negative Regulator of the Wnt Signaling Pathway Mediates Protective Effects in BRCA1 Mutant Breast Cancer.International journal of molecular sciences · 2023Article
- CD146 is closely associated with the prognosis and molecular features of osteosarcoma: Guidance for personalized clinical treatment.Frontiers in genetics · 2022Article
- Near-infrared photoimmunotherapy: design and potential applications for cancer treatment and beyond.Theranostics · 2022Review
- A network pharmacology approach to evaluate the synergistic effect of dihydromyricetin and myricitrin in vine tea on the proliferation of B16F10 cells.Frontiers in nutrition · 2022Article
- Inflammatory cell-associated tumors. Not only macrophages (TAMs), fibroblasts (TAFs) and neutrophils (TANs) can infiltrate the tumor microenvironment. The unique role of tumor associated platelets (TAPs).Cancer immunology, immunotherapy : CII · 2021Review
- Coagulation Signaling through PAR1 as a Therapeutic Target in Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2021Review
- Up-Regulation of CD146 in Schwann Cells Following Peripheral Nerve Injury Modulates Schwann Cell Function in Regeneration.Frontiers in cellular neuroscience · 2021Article
- Prevention of Melanoma Extravasation as a New Treatment Option Exemplified by p38/MK2 Inhibition.International journal of molecular sciences · 2020Article
- Fibronectin in Cancer: Friend or Foe.Cells · 2019Review
- CD146-Targeted Multimodal Image-Guided Photoimmunotherapy of Melanoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2019Article
- Platelet activating factor receptor antagonists improve the efficacy of experimental chemo- and radiotherapy.Clinics (Sao Paulo, Brazil) · 2018Review
- Protease-activated receptor 1 activation enhances doxorubicin-induced cardiotoxicity.Journal of molecular and cellular cardiology · 2018Article
- Emerging Biomarkers in Cutaneous Melanoma.Molecular diagnosis & therapy · 2018Review
- Review
- Antiplatelet agents for cancer treatment: a real perspective or just an echo from the past?Cancer metastasis reviews · 2017Article
- A Review on Platelet Activating Factor Inhibitors: Could a New Class of Potent Metal-Based Anti-Inflammatory Drugs Induce Anticancer Properties?Bioinorganic chemistry and applications · 2017Review
- TGFβ upregulates PAR-1 expression and signalling responses in A549 lung adenocarcinoma cells.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
The cellular and molecular pathways that regulate platelet activation, blood coagulation, and inflammation are emerging as critical players in cancer progression and metastasis. Here, we demonstrate a novel signaling mechanism whereby protease-activated receptor 1 (PAR1) mediates expression of melanoma cell adhesion molecule MCAM/MUC18 (MUC18), a critical marker of melanoma metastasis, via activation of platelet-activating factor receptor (PAFR) and cAMP-responsive element-binding protein (CREB). We found that PAR1 silencing with small hairpin RNA inhibits MUC18 expression in metastatic melanoma cells by inhibiting CREB phosphorylation, activity, and binding to the MUC18 promoter. We further demonstrate that the PAF/PAFR pathway mediates MUC18 expression downstream of PAR1. Indeed, PAR1 silencing down-regulates PAFR expression and PAF production, PAFR silencing blocks MUC18 expression, and re-expression of PAFR in PAR1-silenced cells rescues MUC18 expression. We further demonstrate that the PAR1-PAFR-MUC18 pathway mediates melanoma cell adhesion to microvascular endothelial cells, transendothelial migration, and metastatic retention in the lungs. Rescuing PAFR expression in PAR1-silenced cells fully restores metastatic phenotype of melanoma, indicating that PAFR plays critical role in the molecular mechanism of PAR1 action. Our results link the two pro-inflammatory G-protein-coupled receptors, PAR1 and PAFR, with the metastatic dissemination of melanoma and suggest that PAR1, PAFR, and MUC18 are attractive therapeutic targets for preventing melanoma metastasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.