ArticleEMBO reports2021
Hepsin regulates TGFβ signaling via fibronectin proteolysis.
Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- The instructive scar - the dynamic role of extracellular matrix in biliary pathophysiology.Disease models & mechanisms · 2026Review
- Smoking behaviour, altered DNA methylation, and heart failure risk: evidence from a prospective cohort and epigenetic Mendelian randomization study.Clinical epigenetics · 2026Article
- In vivo modeling of lethal congenital contracture syndrome 1 suggests pathomechanisms in cellular stress responses.The FEBS journal · 2025Article
- Exploring the role of hepsin in prostate cancer: bioinformatics, molecular Docking and molecular dynamics simulations.Discover oncology · 2025Article
- Article
- Inhibiting fibronectin assembly in the breast tumor microenvironment increases cell death and improves response to doxorubicin.bioRxiv : the preprint server for biology · 2025Article
- Hepsin promotes breast tumor growth signaling via the TGFβ-EGFR axis.Molecular oncology · 2024Article
- Baseline Values of Circulating IL-6 and TGF-β Might Identify Patients with HNSCC Who Do Not Benefit from Nivolumab Treatment.Cancers · 2023Article
- Inhibition of the extracellular enzyme A disintegrin and metalloprotease with thrombospondin motif 4 prevents cardiac fibrosis and dysfunction.Cardiovascular research · 2023Article
- Type II Transmembrane Serine Proteases as Modulators in Adipose Tissue Phenotype and Function.Biomedicines · 2023Review
- The POR rs10954732 polymorphism decreases susceptibility to hepatocellular carcinoma and hepsin as a prognostic biomarker correlated with immune infiltration based on proteomics.Journal of translational medicine · 2022Article
- TGF-Frontiers in genetics · 2022Article
- Hepsin regulates TGFβ signaling via fibronectin proteolysis.EMBO reports · 2021Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor-beta (TGFβ) is a multifunctional cytokine with a well-established role in mammary gland development and both oncogenic and tumor-suppressive functions. The extracellular matrix (ECM) indirectly regulates TGFβ activity by acting as a storage compartment of latent-TGFβ, but how TGFβ is released from the ECM via proteolytic mechanisms remains largely unknown. In this study, we demonstrate that hepsin, a type II transmembrane protease overexpressed in 70% of breast tumors, promotes canonical TGFβ signaling through the release of latent-TGFβ from the ECM storage compartment. Mammary glands in hepsin CRISPR knockout mice showed reduced TGFβ signaling and increased epithelial branching, accompanied by increased levels of fibronectin and latent-TGFβ1, while overexpression of hepsin in mammary tumors increased TGFβ signaling. Cell-free and cell-based experiments showed that hepsin is capable of direct proteolytic cleavage of fibronectin but not latent-TGFβ and, importantly, that the ability of hepsin to activate TGFβ signaling is dependent on fibronectin. Altogether, this study demonstrates a role for hepsin as a regulator of the TGFβ pathway in the mammary gland via a novel mechanism involving proteolytic downmodulation of fibronectin.
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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.