ArticleOncotarget2016
Proteinase-activated receptor 2 promotes TGF-β-dependent cell motility in pancreatic cancer cells by sustaining expression of the TGF-β type I receptor ALK5.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 34 citations in OpenAlex.
- COPB2 drives gastric cancer progression via PI3K/AKT/NF-κB signaling: a multi-omics and functional study.Cell adhesion & migration · 2026Article
- Protease-Activated Receptor-2 as a Proteolytic Rheostat in Colorectal and Pancreatic Cancer: From Mechanism to Biomarker-Guided Therapy.International journal of molecular sciences · 2026Review
- RHOV Is a Detachment-Responsive Rho GTPase Necessary for Ovarian Cancer Peritoneal Metastasis.Cancer research · 2026Article
- Orally Administered Rhamnan Sulfate fromMarine drugs · 2026Article
- Hepatocyte KCTD17-mediated SERPINA3 inhibition determines liver fibrosis in metabolic dysfunction-associated steatohepatitis.Experimental & molecular medicine · 2025Article
- Smad transcription factors as mediators of 7 transmembrane G protein-coupled receptor signalling.Acta pharmacologica Sinica · 2025Review
- Bioinformatics and experimental insights into F2RL1 as a key biomarker in cervical cancer diagnosis and prognosis.Scientific reports · 2025Article
- Effects of DOACs on Mouse Melanoma Metastasis and the Inhibitory Mechanism of Edoxaban, a Factor Xa-Specific DOAC.TH open : companion journal to thrombosis and haemostasis · 2025Article
- Identification of key regulators in pancreatic ductal adenocarcinoma using network theoretical approach.PloS one · 2025Article
- Article
- Long non-coding RNA AC245100.4 contributes to prostate cancer migration via regulating PAR2 and activating p38-MAPK pathway.Medical oncology (Northwood, London, England) · 2022Article
- Renal tubular PAR2 promotes interstitial fibrosis by increasing inflammatory responses and EMT process.Archives of pharmacal research · 2022Article
- The Small GTPase RAC1B: A Potent Negative Regulator of-and Useful Tool to Study-TGFβ Signaling.Cancers · 2020Review
- Integrated Analyses Identify Immune-Related Signature Associated with Qingyihuaji Formula for Treatment of Pancreatic Ductal Adenocarcinoma Using Network Pharmacology and Weighted Gene Co-Expression Network.Journal of immunology research · 2020Article
- RAC1B: A Guardian of the Epithelial Phenotype and Protector Against Epithelial-Mesenchymal Transition.Cells · 2019Article
- Proteinase-activated receptor-2 enhances Bcl2-like protein-12 expression in lung cancer cells to suppress p53 expression.Archives of medical science : AMS · 2019Article
- Article
- PAR2 Inhibition Enhanced the Sensitivity of Colorectal Cancer Cells to 5-FU and Reduced EMT Signaling.Oncology research · 2019Article
- Article
- CAFs and TGF-β Signaling Activation by Mast Cells Contribute to Resistance to Gemcitabine/Nabpaclitaxel in Pancreatic Cancer.Cancers · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is characterized by high expression of transforming growth factor (TGF)-β and the G protein-coupled receptor proteinase-activated receptor 2 (PAR2), the latter of which functions as a cell-surface sensor for serine proteinases asscociated with the tumour microenvironment. Since TGF-β and PAR2 affect tumourigenesis by regulating migration, invasion and metastasis, we hypothesized that there is signalling crosstalk between them. Depleting PDAC and non-PDAC cells of PAR2 by RNA interference strongly decreased TGF-β1-induced activation of Smad2/3 and p38 mitogen-activated protein kinase, Smad dependent transcriptional activity, expression of invasion associated genes, and cell migration/invasion in vitro. Likewise, the plasminogen activator-inhibitor 1 gene in primary cultures of aortic smooth muscle cells from PAR2-/- mice displayed a greatly attenuated sensitivity to TGF-β1 stimulation. PAR2 depletion in PDAC cells resulted in reduced protein and mRNA levels of the TGF-β type I receptor activin receptor-like kinase 5 (ALK5). Forced expression of wild-type ALK5 or a kinase-active ALK5 mutant, but not a kinase-active but Smad-binding defective ALK5 mutant, was able to rescue TGF-β1-induced Smad3 activation, Smad dependent transcription, and cell migration in PAR2-depleted cells. Together, our data show that PAR2 is crucial for TGF-β1-induced cell motility by its ability to sustain expression of ALK5. Therapeutically targeting PAR2 may thus be a promising approach in preventing TGF-β-dependent driven metastatic dissemination in PDAC and possibly other stroma-rich tumour types.
Indexed as
Identifiers
What OpenQuestion holds
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.