ArticleeLife2019
KLK3/PSA and cathepsin D activate VEGF-C and VEGF-D.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- Cardiac lymphatic dysfunction and repair in cardiovascular disease.Nature reviews. Cardiology · 2026Review
- Angiogenic Doping: Plausible Yet Difficult to Detect.Sports medicine (Auckland, N.Z.) · 2026Review
- Biopsychosocial trajectories in older adults with planned intensive care: a protocol for a prospective observational study (GeriICU).BMJ open · 2026Article
- Cathepsins in prostate cancer: multifunctional regulators in tumor progression and therapeutic prospects-a narrative review.Translational andrology and urology · 2026Review
- Comprehensive Biochemical Insights into Prostate-Specific Antigen: From Biomarker to Functional Mediator in Prostate Cancer Pathophysiology.Anti-cancer agents in medicinal chemistry · 2026Review
- Elucidating the Potential Targets and Mechanisms of Bisphenol A-Induced Prostate Cancer Based on Network Toxicology and Molecular Docking Analyses.Oncology research · 2026Article
- Cathepsins: Emerging targets in the tumor ecosystem to overcome cancers.Seminars in cancer biology · 2025Review
- Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives.Signal transduction and targeted therapy · 2025Review
- Review
- A PSA SNP associates with cellular function and clinical outcome in men with prostate cancer.Nature communications · 2024Article
- The many roles of cathepsins in restenosis.Heliyon · 2024Article
- Vascular Endothelial Growth Factor-D (VEGF-D): An Angiogenesis Bypass in Malignant Tumors.International journal of molecular sciences · 2023Review
- Article
- The roles of proteases in prostate cancer.IUBMB life · 2023Review
- Exosomal cargos-mediated metabolic reprogramming in tumor microenvironment.Journal of experimental & clinical cancer research : CR · 2023Review
- Biomarkers or biotargets? Using competition to lure cancer cells into evolutionary traps.Evolution, medicine, and public health · 2023Article
- Identifying driver modules based on multi-omics biological networks in prostate cancer.IET systems biology · 2022Article
- Bioactive VEGF-C from E. coli.Scientific reports · 2022Article
- Effects of Hypoxia on RNA Cargo in Extracellular Vesicles from Human Adipose-Derived Stromal/Stem Cells.International journal of molecular sciences · 2022Article
- High Expression of the Lysosomal Protease Cathepsin D Confers Better Prognosis in Neuroblastoma Patients by Contrasting EGF-Induced Neuroblastoma Cell Growth.International journal of molecular sciences · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Vascular endothelial growth factor-C (VEGF-C) acts primarily on endothelial cells, but also on non-vascular targets, for example in the CNS and immune system. Here we describe a novel, unique VEGF-C form in the human reproductive system produced via cleavage by kallikrein-related peptidase 3 (KLK3), aka prostate-specific antigen (PSA). KLK3 activated VEGF-C specifically and efficiently through cleavage at a novel N-terminal site. We detected VEGF-C in seminal plasma, and sperm liquefaction occurred concurrently with VEGF-C activation, which was enhanced by collagen and calcium binding EGF domains 1 (CCBE1). After plasmin and ADAMTS3, KLK3 is the third protease shown to activate VEGF-C. Since differently activated VEGF-Cs are characterized by successively shorter N-terminal helices, we created an even shorter hypothetical form, which showed preferential binding to VEGFR-3. Using mass spectrometric analysis of the isolated VEGF-C-cleaving activity from human saliva, we identified cathepsin D as a protease that can activate VEGF-C as well as VEGF-D.
Indexed as
Identifiers
What OpenQuestion holds
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.