ArticleSignal transduction and targeted therapy2021
CD147 receptor is essential for TFF3-mediated signaling regulating colorectal cancer progression.
Article in Signal transduction and targeted therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 77 citations in OpenAlex.
- Elucidating targets and mechanisms of dietary mycotoxin carcinogenesis via network toxicology, pan-cancer analysis, and molecular simulation.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Unveiling medication patterns in traditional Chinese medicine for the prevention of colorectal cancer recurrence: from potential combinations to validation of components and targets.Chinese medicine · 2026Article
- CD147 promotes NSCLC metastasis by inducing secretory autophagy-dependent exosome secretion via TRIM56-mediated ubiquitination and degradation of GCN2.Cell death and differentiation · 2026Article
- Genetic attenuation of ALDH1A1 increases metastatic potential and aggressiveness in colorectal cancer.Molecular oncology · 2026Article
- Reprogramming the tumor microenvironment via TFF3 targeting: a potential novel avenue to boost CAR-T cell therapy in solid tumors.Cancer gene therapy · 2026Review
- FAM107A Inhibits the Growth, Invasion and Aerobic Glycolysis of LUAD Cells by Regulating CRYAB/PI3K/AKT.Biochemical genetics · 2026Article
- CD147/Basigin: From Integrative Molecular Hub to Translational Therapeutic Target.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Lactate metabolism and protein lactylation in colorectal cancer: from metabolic reprogramming to epigenetic regulation.Frontiers in oncology · 2026Review
- Lymph Node Metastasis-Associated Spatiotemporal Mapping of the TFF3-Linked Niche in Breast Cancer: Integrating Radiogenomic Signatures with Immune-Ecosystem Remodeling.Research (Washington, D.C.) · 2026Article
- TFF3 sensitizes cervical carcinoma cells to cisplatin toxicity by binding to IGF2R.Cancer gene therapy · 2026Article
- A single-cell atlas reveals the tumorigenesis and microenvironment status of primary tracheobronchial tumors.NPJ precision oncology · 2025Article
- A CD147-targeted small-molecule inhibitor potentiates gemcitabine efficacy by triggering ferroptosis in pancreatic ductal adenocarcinoma.Cell reports. Medicine · 2025Article
- Inhibition of TFF3 improves the infiltration and function of CD8International journal of colorectal disease · 2025Article
- Article
- Glycolysis-Driven Prognostic Model for Acute Myeloid Leukemia: Insights into the Immune Landscape and Drug Sensitivity.Biomedicines · 2025Article
- Inhibition of TFF3 synergizes with c-MET inhibitors to decrease the CSC-like phenotype and metastatic burden in ER+HER2+ mammary carcinoma.Cell death & disease · 2025Article
- miR-141-3p inhibited BPA-induced proliferation and migration of lung cancer cells through PTGER4.Cytotechnology · 2025Article
- CD147 at the crossroads of glycoprotein networks, metabolic reprogramming, and metastatic progression.Frontiers in immunology · 2025Review
- Establishing a Prognostic Model Correlates to Inflammatory Response Pathways for Prostate Cancer via Multiomic Analysis of Lactylation-Related Genes.International journal of genomics · 2025Article
- The role of COX2 deficiency attenuates cardiac damage in acute myocardial infarction.BMC cardiovascular disorders · 2024Article
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Authors and funding
24 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Major gaps in understanding the molecular mechanisms of colorectal cancer (CRC) progression and intestinal mucosal repair have hampered therapeutic development for gastrointestinal disorders. Trefoil factor 3 (TFF3) has been reported to be involved in CRC progression and intestinal mucosal repair; however, how TFF3 drives tumors to become more aggressive or metastatic and how TFF3 promotes intestinal mucosal repair are still poorly understood. Here, we found that the upregulated TFF3 in CRC predicted a worse overall survival rate. TFF3 deficiency impaired mucosal restitution and adenocarcinogenesis. CD147, a membrane protein, was identified as a binding partner for TFF3. Via binding to CD147, TFF3 enhanced CD147-CD44s interaction, resulting in signal transducer and activator of transcription 3 (STAT3) activation and prostaglandin G/H synthase 2 (PTGS2) expression, which were indispensable for TFF3-induced migration, proliferation, and invasion. PTGS2-derived PGE2 bound to prostaglandin E2 receptor EP4 subtype (PTGER4) and contributed to TFF3-stimulated CRC progression. Solution NMR studies of the TFF3-CD147 interaction revealed the key residues critical for TFF3 binding and the induction of PTGS2 expression. The ability of TFF3 to enhance mucosal restitution was weakened by a PTGS2 inhibitor. Blockade of TFF3-CD147 signaling using competitive inhibitory antibodies or a PTGS2 inhibitor reduced CRC lung metastasis in mice. Our findings bring strong evidence that CD147 is a novel receptor for TFF3 and PTGS2 signaling is critical for TFF3-induced mucosal restitution and CRC progression, which widens and deepens the understanding of the molecular function of trefoil factors.
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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.