ArticleOncogene2015
Fibulin-3 is a novel TGF-β pathway inhibitor in the breast cancer microenvironment.
Article in Oncogene, 2015. 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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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- Fibulin-7 in progenitor cells promotes adipose tissue fibrosis and disrupts metabolic homeostasis in obesity.Protein & cell · 2026Article
- Proteomic analysis of liver fibrosis reveals EFEMP1 as a new modulator of focal adhesion and migration of hepatic stellate cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Targeting the Key Signaling Pathways in Breast Cancer: From Molecular Mechanism to Therapeutic Interventions.Recent patents on anti-cancer drug discovery · 2025Review
- [Fibulin-3 Regulates Tissue Inhibitor of Metalloproteinases 3 to Inhibit Senescence in Intervertebral Disc Nucleus Pulposus Cells].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Article
- EFEMP1 haploinsufficiency causes a Marfan-like hereditary connective tissue disorder.American journal of medical genetics. Part A · 2024Article
- EFEMP1 binds to STEAP1 to promote osteosarcoma proliferation and invasion via the Wnt/β-catenin and TGF-β/Smad2/3 signal pathways.Journal of bone oncology · 2022Article
- Role of Fibulins in Embryonic Stage Development and Their Involvement in Various Diseases.Biomolecules · 2021Review
- Fibulin-3 knockout mice demonstrate corneal dysfunction but maintain normal retinal integrity.Journal of molecular medicine (Berlin, Germany) · 2020Article
- miR-9-Mediated Inhibition ofCells · 2020Article
- The Pathophysiological Significance of Fibulin-3.Biomolecules · 2020Review
- Correlation of Fibulin-2 expression with proliferation, migration and invasion of breast cancer cells.Oncology letters · 2020Article
- EFEMP1 as a Potential Biomarker for Diagnosis and Prognosis of Osteosarcoma.BioMed research international · 2020Article
- WidespreadGenome research · 2019Article
- Overexpression of mircoRNA-137 inhibits cervical cancer cell invasion, migration and epithelial-mesenchymal transition by suppressing the TGF-β/smad pathway via binding to GREM1.Cancer cell international · 2019Article
- Novel Associations Within the Tumor Microenvironment: Fibulins Meet ADAMTSs.Frontiers in oncology · 2019Review
- EFEMP2 Inhibits Breast Cancer Invasion And Metastasis In Vitro And In Vivo.OncoTargets and therapy · 2019Article
- Extracellular Interactions between Fibulins and Transforming Growth Factor (TGF)-β in Physiological and Pathological Conditions.International journal of molecular sciences · 2018Review
- A genome-wide association study identifies a susceptibility locus for biliary atresia on 2p16.1 within the gene EFEMP1.PLoS genetics · 2018Article
- Fibulin-3 knockdown inhibits cervical cancer cell growth and metastasis in vitro and in vivo.Scientific reports · 2018Article
- Fibulin-3 promotes muscle-invasive bladder cancer.Oncogene · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Transforming growth factor-β (TGF-β) is an important regulator of breast cancer progression. However, how the breast cancer microenvironment regulates TGF-β signaling during breast cancer progression remains largely unknown. Here, we identified fibulin-3 as a secreted protein in the breast cancer microenvironment, which efficiently inhibits TGF-β signaling in both breast cancer cells and endothelial cells. Mechanistically, fibulin-3 interacts with the type I TGF-β receptor (TβRI) to block TGF-β induced complex formation of TβRI with the type II TGF-β receptor (TβRII) and subsequent downstream TGF-β signaling. Fibulin-3 expression decreases during breast cancer progression, with low fibulin-3 levels correlating with a poorer prognosis. Functionally, high fibulin-3 levels inhibited TGF-β-induced epithelial-mesenchymal transition (EMT), migration, invasion and endothelial permeability, while loss of fibulin-3 expression/function promoted these TGF-β-mediated effects. Further, restoring fibulin-3 expression in breast cancer cells inhibited TGF-β signaling, breast cancer cell EMT, invasion and metastasis in vivo. These studies provide a novel mechanism for how TGF-β signaling is regulated by the tumor microenvironment, and provide insight into targeting the TGF-β signaling pathway in human breast cancer patients.
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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.