ArticleInternational journal of molecular sciences2017
The Role of PAR2 in TGF-β1-Induced ERK Activation and Cell Motility.
Article in International journal of molecular sciences, 2017. 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, 25 citations in OpenAlex.
- Targeting PAR-2-driven inflammatory pathways in colorectal cancer: mechanistic insights from atorvastatin and rosuvastatin treatment in cell line models.Translational cancer research · 2025Article
- Protease-activated receptors in vascular smooth muscle cells: a bridge between thrombo-inflammation and vascular remodelling.Cell communication and signaling : CCS · 2025Review
- Significance of FXa and its receptor PAR2 for the growth of colon cancer cellsFrontiers in oncology · 2025Article
- Kallikrein-Related Peptidase 6 Contributes to Murine Intestinal Tumorigenesis Driven by a MutantCancers · 2024Article
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- A deep tabular data learning model predicting cisplatin sensitivity identifies BCL2L1 dependency in cancer.Computational and structural biotechnology journal · 2023Article
- Diversification of PAR signaling through receptor crosstalk.Cellular & molecular biology letters · 2022Review
- Lean body mass predicts postoperative liver failure in patients with hepatocellular carcinoma.Cancer biomarkers : section A of Disease markers · 2022Article
- Cardio-Oncology: Understanding the Intersections Between Cardiac Metabolism and Cancer Biology.JACC. Basic to translational science · 2021Review
- Dabigatran mitigates cisplatin-mediated nephrotoxicity through down regulation of thrombin pathway.Journal of advanced research · 2021Article
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- The Effects of Prebiotic Supplementation with OMNi-LOGiCNutrients · 2020Article
- Cancer Cachexia and Related Metabolic Dysfunction.International journal of molecular sciences · 2020Review
- Transforming growth factor beta 1 impairs benign prostatic luminal epithelial cell monolayer barrier function.American journal of clinical and experimental urology · 2020Article
- Collagenolytic matrix metalloproteinases antagonize proteinase-activated receptor-2 activation, providing insights into extracellular matrix turnover.The Journal of biological chemistry · 2019Article
- Regulation of TGF-β1 on PI3KC3 and its role in hypertension-induced vascular injuries.Experimental and therapeutic medicine · 2019Article
- Membrane-Anchored Serine Proteases and Protease-Activated Receptor-2-Mediated Signaling: Co-Conspirators in Cancer Progression.Cancer research · 2019Review
- The role of contextual signal TGF-β1 inducer of epithelial mesenchymal transition in metastatic lung adenocarcinoma patients with brain metastases: an update on its pathological significance and therapeutic potential.Contemporary oncology (Poznan, Poland) · 2019Review
- TINAGL1 promotes hepatocellular carcinogenesis through the activation of TGF-β signaling-medicated VEGF expression.Cancer management and research · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRecently, the expression of proteinase-activated receptor 2 (PAR2) has been shown to be essential for activin receptor-like kinase 5 (ALK5)/SMAD-mediated signaling and cell migration by transforming growth factor (TGF)-β1. However, it is not known whether activation of non-SMAD TGF-β signaling (e.g., RAS-RAF-MEK-extracellular signal-regulated kinase (ERK) signaling) is required for cell migration and whether it is also dependent on PAR2.
methodsRNA interference was used to deplete cells of PAR2, followed by xCELLigence technology to measure cell migration, phospho-immunoblotting to assess ERK1/2 activation, and co-immunoprecipitation to detect a PAR2-ALK5 physical interaction.
resultsInhibition of ERK signaling with the MEK inhibitor U0126 blunted the ability of TGF-β1 to induce migration in pancreatic cancer Panc1 cells. ERK activation in response to PAR2 agonistic peptide (PAR2-AP) was strong and rapid, while it was moderate and delayed in response to TGF-β1. Basal and TGF-β1-dependent ERK, but not SMAD activation, was blocked by U0126 in Panc1 and other cell types indicating that ERK activation is downstream or independent of SMAD signaling. Moreover, cellular depletion of PAR2 in HaCaT cells strongly inhibited TGF-β1-induced ERK activation, while the biased PAR2 agonist GB88 at 10 and 100 µM potentiated TGF-β1-dependent ERK activation and cell migration. Finally, we provide evidence for a physical interaction between PAR2 and ALK5. Our data show that both PAR2-AP- and TGF-β1-induced cell migration depend on ERK activation, that PAR2 expression is crucial for TGF-β1-induced ERK activation, and that the functional cooperation of PAR2 and TGF-β1 involves a physical interaction between PAR2 and ALK5.
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