ArticleJCI insight2023
Stabilization of E-cadherin adhesions by COX-2/GSK3β signaling is a targetable pathway in metastatic breast cancer.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
- Cyclooxygenase-2 selective inhibitors in cancer prevention and therapy: inflammopharmacological basis and translational prospects.Medical oncology (Northwood, London, England) · 2026Review
- USF2-Mediated APOE-Cholesterol Signaling Promotes CTC Clustering and Metastasis in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2026Article
- Article
- Metabolic maintenance of breast cancer cells and metastases through E-cadherin/YAP-dependent pyruvate carboxylase expression.bioRxiv : the preprint server for biology · 2026Article
- ACSL5 Mediates Adaptation to the Palmitic Acid-Enriched Pulmonary Microenvironment to Enhance Metastatic Breast Cancer Cell Survival and Lung Metastasis.Cancer research · 2026Article
- Elucidating the potential mechanism of short-chain chlorinated paraffins in breast cancer via computational prediction integrating network toxicology and molecular docking.Scientific reports · 2026Article
- 3D "Emboli" Culture Models Epithelial Breast Cancer Cell Oxidative Mitochondrial Metabolism with Relevance for Lung Metastasis.Cancer research communications · 2026Article
- LITAF suppresses breast cancer and paclitaxel resistance by ubiquitinating and degrading PCMT1 to inhibit COX-2-dependent arachidonic acid metabolism.Frontiers in pharmacology · 2026Article
- Identification of potential vinorelbine-associated prognostic genes in breast cancer through integrative bioinformatics and experimental validation.Frontiers in oncology · 2026Article
- Crocus sativus L.-derived lauric acid-functionalized gold nanoparticles induce ferroptosis in HeLa cells and reverse M2 macrophage polarization via the PGE2/EP2/cAMP-PKA signaling pathway: a network pharmacology-based study.Frontiers in pharmacology · 2026Article
- SLC41A2 Suppresses Colon Cancer Progression by Inhibiting GSK3β Ubiquitin-proteasome Degradation.Current molecular medicine · 2026Article
- Triptonide-mediated PTGS2 Inhibition Induces Autophagic Cell Death to Suppress the Progression of Triple-negative Breast Cancer and Epithelial Ovarian Cancer.International journal of biological sciences · 2026Article
- Celastrol increases anoikis sensitivity to suppress triple-negative breast cancer via EGFR pathway and p-EMT state regulation.Frontiers in pharmacology · 2026Article
- Assessment of Imaging Mass Cytometry (IMC) as a Tool to Characterize Circulating Tumor Cells (CTCs) in Preclinical Mouse Models.bioRxiv : the preprint server for biology · 2025Article
- Cancer Reversion Therapy: Prospects, Progress and Future Directions.Current issues in molecular biology · 2025Review
- Decoding intratumoral cyclooxygenase-2 signaling through multi-omics: insights from esophageal cancer and beyond.Clinical and experimental medicine · 2025Article
- The E3 ligase HECTD4 regulates COX-2-dependent tumor progression and metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Erianin induces apoptosis of osteosarcoma cells through ferroptosis signaling pathway, and inhibits proliferation and migration of osteosarcoma cells.Cytotechnology · 2025Article
- LncRNA LOC610012 Inhibits Canine Mammary Tumor Activity via the PTGS2/EP3 and GSK3β Signaling Pathways.Cells · 2025Article
- Three-Dimensional Culture Systems in Neuroblastoma Research.Organoids · 2025Article
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Metastatic progression of epithelial cancers can be associated with epithelial-mesenchymal transition (EMT) including transcriptional inhibition of E-cadherin (CDH1) expression. Recently, EM plasticity (EMP) and E-cadherin-mediated, cluster-based metastasis and treatment resistance have become more appreciated. However, the mechanisms that maintain E-cadherin expression in this context are less understood. Through studies of inflammatory breast cancer (IBC) and a 3D tumor cell "emboli" culture paradigm, we discovered that cyclooxygenase 2 (COX-2; PTGS2), a target gene of C/EBPδ (CEBPD), or its metabolite prostaglandin E2 (PGE2) promotes protein stability of E-cadherin, β-catenin, and p120 catenin through inhibition of GSK3β. The COX-2 inhibitor celecoxib downregulated E-cadherin complex proteins and caused cell death. Coexpression of E-cadherin and COX-2 was seen in breast cancer tissues from patients with poor outcome and, along with inhibitory GSK3β phosphorylation, in patient-derived xenografts (PDX) including triple negative breast cancer (TNBC).Celecoxib alone decreased E-cadherin protein expression within xenograft tumors, though CDH1 mRNA levels increased, and reduced circulating tumor cell (CTC) clusters. In combination with paclitaxel, celecoxib attenuated or regressed lung metastases. This study has uncovered a mechanism by which metastatic breast cancer cells can maintain E-cadherin-mediated cell-to-cell adhesions and cell survival, suggesting that some patients with COX-2+/E-cadherin+ breast cancer may benefit from targeting of the PGE2 signaling pathway.
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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.