ArticleFrontiers in pharmacology2021
Targeting PAR2 Overcomes Gefitinib Resistance in Non-Small-Cell Lung Cancer Cells Through Inhibition of EGFR Transactivation.
Article in Frontiers in pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Protease-Activated Receptor-2 Promotes Metastasis: An Emerging Therapeutic Target.Molecular cancer research : MCR · 2026Review
- G protein-coupled receptors as novel therapeutic targets in non-small-cell lung cancer.Medical review (2021) · 2025Review
- PAR2 regulates proliferation, migration of lung cancer and chemotherapy sensitivity by involving PTEN pathway.Future science OA · 2025Article
- Navigating Glioma Complexity: The Role of Abnormal Signaling Pathways in Shaping Future Therapies.Biomedicines · 2025Review
- The Punicalagin Compound Mitigates Bronchial Epithelial Cell Senescence Induced by Cigarette Smoke Extract through the PAR2/mTOR Pathway.Current medicinal chemistry · 2025Article
- TET3-mediated DNA demethylation modification activates SHP2 expression to promote endometrial cancer progression through the EGFR/ERK pathway.Journal of gynecologic oncology · 2024Article
- Update on protease-activated receptor 2 in inflammatory and autoimmune dermatological diseases.Frontiers in immunology · 2024Review
- Computational identification and experimental verification of a novel signature based on SARS-CoV-2-related genes for predicting prognosis, immune microenvironment and therapeutic strategies in lung adenocarcinoma patients.Frontiers in immunology · 2024Article
- PAR2 promotes malignancy in lung adenocarcinoma.American journal of translational research · 2024Article
- Photonanozyme-Kras-ribosome combination treatment of non-small cell lung cancer after COVID-19.Frontiers in immunology · 2024Review
- Protease-activated receptor 2 attenuates doxorubicin-induced apoptosis in colon cancer cells.Journal of cell communication and signaling · 2023Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- [Research Progress on Pathogenic Mechanism and Potential Therapeutic Drugs of Idiopathic Pulmonary Fibrosis Complicated with Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2022Article
- Radiomics signature: A potential biomarker for β-arrestin1 phosphorylation prediction in hepatocellular carcinoma.World journal of gastroenterology · 2022Article
- Transmembrane serine protease 2 is a prognostic factor for lung adenocarcinoma.International journal of oncology · 2022Article
- Heat Shock Protein 90 (HSP90) Inhibitors as Anticancer Medicines: A Review on the Computer-Aided Drug Discovery Approaches over the Past Five Years.Computational and mathematical methods in medicine · 2022Review
- A Novel Small-Molecule Inhibitor of SREBP-1 Based on Natural Product Monomers Upregulates the Sensitivity of Lung Squamous Cell Carcinoma Cells to Antitumor Drugs.Frontiers in pharmacology · 2022Article
- Cabozantinib Is Effective in Melanoma Brain Metastasis Cell Lines and Affects Key Signaling Pathways.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug resistance can notably restrict clinical applications of gefitinib that is a commonly used EGFR-tyrosine kinase inhibitors (EGFR-TKIs) for non-small cell lung cancer (NSCLC). The attempts in exploring novel drug targets and reversal strategies are still needed, since gefitinib resistance has not been fully addressed. Protease-activated receptor 2 (PAR2), a G protein-coupled receptor, possesses a transactivation with EGFR to initiate a variety of intracellular signal transductions, but there is a lack of investigations on the role of PAR2 in gefitinib resistance. This study established that protease-activated receptor 2 (PAR2), actively participated in NSCLC resistant to gefitinib. PAR2 expression was significantly up-regulated when NSCLC cells or tumor tissues became gefitinib resistance. PAR2 inhibition notably enhanced gefitinib to modulate EGFR transactivation, cell viability, migration and apoptosis in gefitinib-sensitive and-resistant NSCLC cells, suggesting its reversal effects in gefitinib resistance. Meanwhile, the combination of a PAR2 inhibitor (P2pal-18S) and gefitinib largely blocked ERK phosphorylation and epithelial-mesenchymal transition (EMT) compared to gefitinib alone. Importantly, we probed its underlying mechanism and uncovered that PAR2 blockade sensitized gefitinib and reversed its resistance mainly via β-arrestin-EGFR-ERK signaling axis. These effects of PAR2 inhibition were further confirmed by the
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