ArticleProceedings of the National Academy of Sciences of the United States of America2011
Protease activated receptor-1 inhibits the Maspin tumor-suppressor gene to determine the melanoma metastatic phenotype.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 46 citations in OpenAlex.
- Integrated Bulk and Single-Cell Transcriptomics Reveals the C3-C3AR1 Axis as a Candidate Mediator of Coagulome-Immune Crosstalk in Osteosarcoma.Biomedicines · 2026Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- Investigation of the Subcellular Localization-Dependent Anti- or Pro-Tumor Functions of Maspin in Human Lung Adenocarcinoma Cell Line.Yonago acta medica · 2022Article
- Integrating the tumor-suppressive activity of Maspin with p53 in retuning the epithelial homeostasis: A working hypothesis and applicable prospects.Frontiers in oncology · 2022Review
- Chimeric Antigen Receptor (CAR) T Cell Therapy for Metastatic Melanoma: Challenges and Road Ahead.Cells · 2021Review
- Modulation of the Complement System by Neoplastic Disease of the Central Nervous System.Frontiers in immunology · 2021Review
- Tissue Factor and Cancer: Regulation, Tumor Growth, and Metastasis.Seminars in thrombosis and hemostasis · 2019Review
- Transcriptional Landscape of PARs in Epithelial Malignancies.International journal of molecular sciences · 2018Review
- Protease-activated receptor-1 impedes prostate and intestinal tumor progression in mice.Journal of thrombosis and haemostasis : JTH · 2018Article
- Protease-activated receptor 1 activation enhances doxorubicin-induced cardiotoxicity.Journal of molecular and cellular cardiology · 2018Article
- Clinical significance of serum Protease-Activated Receptor-1 (PAR-1) levels in patients with cutaneous melanoma.BBA clinical · 2016Article
- Protease-Activated Receptors and other G-Protein-Coupled Receptors: the Melanoma Connection.Frontiers in genetics · 2016Review
- Contributions of thrombin targets to tissue factor-dependent metastasis in hyperthrombotic mice.Journal of thrombosis and haemostasis : JTH · 2014Article
- Harnessing the genome for characterization of G-protein coupled receptors in cancer pathogenesis.The FEBS journal · 2013Review
- Role of maspin in cancer.Clinical and translational medicine · 2013Article
- Tissue factor and cancer.Thrombosis research · 2012Review
- GPCRs and cancer.Acta pharmacologica Sinica · 2012Review
- PAR-1 and thrombin: the ties that bind the microenvironment to melanoma metastasis.Cancer research · 2011Review
- Expression and function of the kallikrein-related peptidase 6 in the human melanoma microenvironment.The Journal of investigative dermatology · 2011Article
- Tissue factor and cell signalling in cancer progression and thrombosis.Journal of thrombosis and haemostasis : JTH · 2011Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The thrombin receptor protease activated receptor-1 (PAR-1) is overexpressed in metastatic melanoma cell lines and tumor specimens. Previously, we demonstrated a significant reduction in tumor growth and experimental lung metastasis after PAR-1 silencing via systemic delivery of siRNA encapsulated into nanoliposomes. Gene expression profiling identified a 40-fold increase in expression of Maspin in PAR-1-silenced metastatic melanoma cell lines. Maspin promoter activity was significantly increased after PAR-1 silencing, suggesting that PAR1 negatively regulates Maspin at the transcriptional level. ChIP analyses revealed that PAR-1 decreases binding of Ets-1 and c-Jun transcription factors to the Maspin promoter, both known to activate Maspin transcription. PAR-1 silencing did not affect Ets-1 or c-Jun expression; rather it resulted in increased expression of the chromatin remodeling complex CBP/p300, as well as decreased activity of the CBP/p300 inhibitor p38, resulting in increased binding of Ets-1 and c-Jun to the Maspin promoter and higher Maspin expression. Functionally, Maspin expression reduced the invasive capability of melanoma cells after PAR-1 silencing, which was abrogated after rescuing with PAR-1. Furthermore, tumor growth and experimental lung metastasis was significantly decreased after expressing Maspin in a metastatic melanoma cell line. Moreover, silencing Maspin in PAR-1-silenced cells reverted the inhibition of tumor growth and experimental lung metastasis. Herein, we demonstrate a mechanism by which PAR-1 negatively regulates the expression of the Maspin tumor-suppressor gene in the acquisition of the metastatic melanoma phenotype, thus attributing an alternative function to PAR-1 other than coagulation.
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