ArticleBreast cancer research : BCR2021
Identification of MFGE8 and KLK5/7 as mediators of breast tumorigenesis and resistance to COX-2 inhibition.
Article in Breast cancer research : BCR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Eganelisib combined with immune checkpoint inhibitor therapy and chemotherapy in frontline metastatic triple-negative breast cancer triggers macrophage reprogramming, immune activation and extracellular matrix reorganization in the tumor microenvironment.Journal for immunotherapy of cancer · 2024Trial
- Cyclooxygenase-2 selective inhibitors in cancer prevention and therapy: inflammopharmacological basis and translational prospects.Medical oncology (Northwood, London, England) · 2026Review
- KLK7 overexpression promotes an aggressive phenotype and facilitates peritoneal dissemination in colorectal cancer cells.FEBS open bio · 2026Article
- ADAMTS-8 and kallikrein-related peptidases 10 and 5 proteases also have a tumor suppression role.World journal of clinical oncology · 2025Review
- Relevance of Cellular Homeostasis-Related Gene Expression Signatures in Distinct Molecular Subtypes of Breast Cancer.Biomedicines · 2025Article
- scVAG: Unified single-cell clustering via variational-autoencoder integration with Graph Attention Autoencoder.Heliyon · 2024Article
- KLK7, KLK10, and KLK11 in Papillary Thyroid Cancer: Bioinformatic Analysis and Experimental Validation.Biochemical genetics · 2024Article
- Lactadherin immunoblockade in small extracellular vesicles inhibits sEV-mediated increase of pro-metastatic capacities.Biological research · 2024Article
- In silico screening, synthesis, characterization and biological evaluation of novel anticancer agents as potential COX-2 inhibitors.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2023Article
- Targeting MFGE8 secreted by cancer-associated fibroblasts blocks angiogenesis and metastasis in esophageal squamous cell carcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Establishment of a prognostic model toward lung squamous cell carcinoma based on mPhysiological genomics · 2023Article
- Chronic Exposure to Nitric Oxide Induces P53 Mutations and Malignant-like Features in Human Breast Epithelial Cells.Biomolecules · 2023Article
- Review
- Proteomic analysis of plasma exosomes in patients with non-small cell lung cancer.Translational lung cancer research · 2022Article
- Remodelling of the tumour microenvironment by the kallikrein-related peptidases.Nature reviews. Cancer · 2022Review
- Lactadherin: From a Well-Known Breast Tumor Marker to a Possible Player in Extracellular Vesicle-Mediated Cancer Progression.International journal of molecular sciences · 2022Review
- Involvement of Mitochondrial Mechanisms and Cyclooxygenase-2 Activation in the Effect of Desethylamiodarone on 4T1 Triple-Negative Breast Cancer Line.International journal of molecular sciences · 2022Article
- IGF2BP3 promotes progression of gallbladder carcinoma by stabilizing KLK5 mRNA in NFrontiers in oncology · 2022Article
- New Insights into the Therapeutic Applications of CRISPR/Cas9 Genome Editing in Breast Cancer.Genes · 2021Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCyclooxygenase 2 (COX-2) promotes stemness in triple negative breast cancer (TNBC), highlighting COX-2 as a promising therapeutic target in these tumors. However, to date, clinical trials using COX-2 inhibitors in breast cancer only showed variable patient responses with no clear significant clinical benefits, suggesting underlying molecular mechanisms contributing to resistance to COX-2 inhibitors.
methodsBy combining in silico analysis of human breast cancer RNA-seq data with interrogation of public patient databases and their associated transcriptomic, genomic, and clinical profiles, we identified COX-2 associated genes whose expression correlate with aggressive TNBC features and resistance to COX-2 inhibitors. We then assessed their individual contributions to TNBC metastasis and resistance to COX-2 inhibitors, using CRISPR gene knockout approaches in both in vitro and in vivo preclinical models of TNBC.
resultsWe identified multiple COX-2 associated genes (TPM4, RGS2, LAMC2, SERPINB5, KLK7, MFGE8, KLK5, ID4, RBP1, SLC2A1) that regulate tumor lung colonization in TNBC. Furthermore, we found that silencing MFGE8 and KLK5/7 gene expression in TNBC cells markedly restored sensitivity to COX-2 selective inhibitor both in vitro and in vivo.
conclusionsTogether, our study supports the establishment and use of novel COX-2 inhibitor-based combination therapies as future strategies for TNBC treatment.
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