ArticleOncogene2015
Non-hematopoietic PAR-2 is essential for matriptase-driven pre-malignant progression and potentiation of ras-mediated squamous cell carcinogenesis.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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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
47 citing papers in PubMed, 66 citations in OpenAlex.
- A start methionine mutation in matriptase causes the membrane anchor to be skipped and replaced by a cryptic signal peptide.The Journal of biological chemistry · 2026Article
- MMP1 and PRSS23 induce PARCommunications biology · 2026Article
- Signaling pathways and targeted interventions for precancers.Signal transduction and targeted therapy · 2026Review
- From Dysplasia to Carcinoma: Expression Patterns of Dermokine, Matriptase, and Tryptase in OPMD.Oral diseases · 2026Article
- KLK5 and KLK7 drive cervical carcinoma via KLK14-dependent RhoA and NF-κB pathways.Translational oncology · 2025Article
- Protease-mediated activation of Par2 elicits calcium waves during zebrafish egg activation and blastomere cleavage.PLoS biology · 2025Article
- GPCR Screening Reveals that the Metabolite Receptor HCAR3 Regulates Epithelial Proliferation, Migration, and Cellular Respiration.The Journal of investigative dermatology · 2024Article
- Matriptase drives dissemination of ovarian cancer spheroids by a PAR-2/PI3K/Akt/MMP9 signaling axis.The Journal of cell biology · 2023Article
- Surfactant protein a attenuates generalized and localized neuroinflammation in neonatal mice.Brain research · 2023Article
- ROS is a master regulator of in vitro matriptase activation.PloS one · 2023Article
- Environment-Sensitive Ectodomain Shedding of Epithin/PRSS14 Increases Metastatic Potential of Breast Cancer Cells by Producing CCL2.Molecules and cells · 2022Article
- Proteases and HPV-Induced Carcinogenesis.Cancers · 2022Review
- Understanding HAIs: Ally proteins in the fight against cancer.The FEBS journal · 2022Article
- Downregulation of Matriptase Inhibits Porphyromonas gingivalis Lipopolysaccharide-Induced Matrix Metalloproteinase-1 and Proinflammatory Cytokines by Suppressing the TLR4/NF-BioMed research international · 2022Article
- Downregulation of matriptase suppresses the PAR‑2/PLCγ2/PKC‑mediated invasion and migration abilities of MCF‑7 breast cancer cells.Oncology reports · 2021Article
- Kallikrein 5 Inhibition by the Lympho-Epithelial Kazal-Type Related Inhibitor Hinders Matriptase-Dependent Carcinogenesis.Cancers · 2021Article
- Matriptase activation of Gq drives epithelial disruption and inflammation via RSK and DUOX.eLife · 2021Article
- Intramembrane proteolysis of an extracellular serine protease, epithin/PRSS14, enables its intracellular nuclear function.BMC biology · 2020Article
- Activation of G-Protein Coupled Receptor-Gαi Signaling Increases Keratinocyte Proliferation and Reduces Differentiation, Leading to Epidermal Hyperplasia.The Journal of investigative dermatology · 2020Article
- Membrane-anchored serine proteases as regulators of epithelial function.Biochemical Society transactions · 2020Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
The membrane-anchored serine protease, matriptase, is consistently dysregulated in a range of human carcinomas, and high matriptase activity correlates with poor prognosis. Furthermore, matriptase is unique among tumor-associated proteases in that epithelial stem cell expression of the protease suffices to induce malignant transformation. Here, we use genetic epistasis analysis to identify proteinase-activated receptor (PAR)-2-dependent inflammatory signaling as an essential component of matriptase-mediated oncogenesis. In cell-based assays, matriptase was a potent activator of PAR-2, and PAR-2 activation by matriptase caused robust induction of nuclear factor (NF)κB through Gαi. Importantly, genetic elimination of PAR-2 from mice completely prevented matriptase-induced pre-malignant progression, including inflammatory cytokine production, inflammatory cell recruitment, epidermal hyperplasia and dermal fibrosis. Selective ablation of PAR-2 from bone marrow-derived cells did not prevent matriptase-driven pre-malignant progression, indicating that matriptase activates keratinocyte stem cell PAR-2 to elicit its pro-inflammatory and pro-tumorigenic effects. When combined with previous studies, our data suggest that dual induction of PAR-2-NFκB inflammatory signaling and PI3K-Akt-mTor survival/proliferative signaling underlies the transforming potential of matriptase and may contribute to pro-tumorigenic signaling in human epithelial carcinogenesis.
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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.