ArticleOncotarget2016
Monomeric gremlin is a novel vascular endothelial growth factor receptor-2 antagonist.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- Gremlin-1 Drives Tumour Vascularization by Promoting Endothelial Differentiation and Angiogenesis.Journal of cellular and molecular medicine · 2026Article
- Penile remodeling, Sonic hedgehog, and fibrosis.The journal of sexual medicine · 2025Article
- Ex.50.T aptamer impairs tumor-stroma cross-talk in breast cancer by targeting gremlin-1.Cell death discovery · 2025Article
- Gremlin1: a BMP antagonist with therapeutic potential in Oncology.Investigational new drugs · 2024Review
- Evaluation of Gremlin-1 as a therapeutic target in metabolic dysfunction-associated steatohepatitis.eLife · 2024Article
- BMP4 and GREM1 are targets of SHH signaling and downstream regulators of collagen in the penis.The journal of sexual medicine · 2024Article
- GREM1 signaling in cancer: tumor promotor and suppressor?Journal of cell communication and signaling · 2023Article
- Metabolic memory in diabetic foot syndrome (DFS): MICRO-RNAS, single nucleotide polymorphisms (SNPs) frequency and their relationship with indices of endothelial function and adipo-inflammatory dysfunction.Cardiovascular diabetology · 2023Article
- Modeling Receptor Motility along Advecting Lipid Membranes.Membranes · 2022Review
- Insights into the Role of Gremlin-1, a Bone Morphogenic Protein Antagonist, in Cancer Initiation and Progression.Biomedicines · 2022Review
- Production and Biochemical Characterization of Dimeric Recombinant Gremlin-1.International journal of molecular sciences · 2022Article
- The BMP Pathway in Blood Vessel and Lymphatic Vessel Biology.International journal of molecular sciences · 2021Review
- Phenotypic Modulation of Macrophages and Vascular Smooth Muscle Cells in Atherosclerosis-Nitro-Redox Interconnections.Antioxidants (Basel, Switzerland) · 2021Review
- COCO/DAND5 inhibits developmental and pathological ocular angiogenesis.EMBO molecular medicine · 2021Article
- Article
- Extracellular BMP Antagonists, Multifaceted Orchestrators in the Tumor and Its Microenvironment.International journal of molecular sciences · 2020Review
- Gremlin mediates the TGF-β-induced induction of profibrogenic genes in human retinal pigment epithelial cells.Experimental and therapeutic medicine · 2020Article
- Construction and Validation of a Robust Cancer Stem Cell-Associated Gene Set-Based Signature to Predict Early Biochemical Recurrence in Prostate Cancer.Disease markers · 2020Article
- Gremlin in the Vitreous of Patients with Proliferative Diabetic Retinopathy and the Downregulation of Gremlin in Retinal Pigment Epithelial Cells.Journal of diabetes research · 2020Article
- No evidence of Gremlin1-mediated activation of VEGFR2 signaling in endothelial cells.The Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Angiogenesis plays a key role in various physiological and pathological conditions, including inflammation and tumor growth. The bone morphogenetic protein (BMP) antagonist gremlin has been identified as a novel pro-angiogenic factor. Gremlin promotes neovascular responses via a BMP-independent activation of the vascular endothelial growth factor (VEGF) receptor-2 (VEGFR2). BMP antagonists may act as covalent or non-covalent homodimers or in a monomeric form, while VEGFRs ligands are usually dimeric. However, the oligomeric state of gremlin and its role in modulating the biological activity of the protein remain to be elucidated.Here we show that gremlin is expressed in vitro and in vivo both as a monomer and as a covalently linked homodimer. Mutagenesis of amino acid residue Cys141 prevents gremlin dimerization leading to the formation of gremlinC141A monomers. GremlinC141A monomer retains a BMP antagonist activity similar to the wild-type dimer, but is devoid of a significant angiogenic capacity. Notably, we found that gremlinC141A mutant engages VEGFR2 in a non-productive manner, thus acting as receptor antagonist. Accordingly, both gremlinC141A and wild-type monomers inhibit angiogenesis driven by dimeric gremlin or VEGF-A165. Moreover, by acting as a VEGFR2 antagonist, gremlinC141A inhibits the angiogenic and tumorigenic potential of murine breast and prostate cancer cells in vivo.In conclusion, our data show that gremlin exists in multiple forms endowed with specific bioactivities and provide new insights into the molecular bases of gremlin dimerization. Furthermore, we propose gremlin monomer as a new inhibitor of VEGFR2 signalling during tumor growth.
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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 Socratic graph.