ArticleNeoplasia (New York, N.Y.)2018
A Heparin Binding Motif Rich in Arginine and Lysine is the Functional Domain of YKL-40.
Article in Neoplasia (New York, N.Y.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Chitinase‑3 like‑protein‑1: A potential predictor of cardiovascular disease (Review).Molecular medicine reports · 2024Pooled it
- Lactylated chitinase-3-like protein 1 promotes the development of sepsis.Central-European journal of immunology · 2026Article
- Elucidating the functional significance of catalytic and chitin-binding domains for the anti-cancer property of a bacterial endochitinase.Journal, genetic engineering & biotechnology · 2025Article
- Article
- Human chitinases and chitinase-like proteins as emerging drug targets - a medicinal chemistry perspective.RSC medicinal chemistry · 2025Review
- Structural and functional significance ofJournal of virology · 2025Article
- Heparin-binding of the human chitinase-like protein YKL-40 is allosterically modified by chitin oligosaccharides.Biochemistry and biophysics reports · 2025Article
- Mechanistic studies on the role of CHI3L1 in eosinophilic inflammation in chronic sinusitis.Frontiers in immunology · 2025Review
- Evaluation of the Recombinant Bacterial Chitinases as Anti-proliferative and Anti-migratory Agents for the Human Breast Cancer Cell Line, MCF-7.Applied biochemistry and biotechnology · 2024Article
- Uncovering novel mechanisms of chitinase-3-like protein 1 in driving inflammation-associated cancers.Cancer cell international · 2024Review
- Prodrug-conjugated tumor-seeking commensals for targeted cancer therapy.Nature communications · 2024Article
- Potential Roles and Future Perspectives of Chitinase 3-like 1 in Macrophage Polarization and the Development of Diseases.International journal of molecular sciences · 2023Review
- Identification of RNF150 as the hub gene associated with microsatellite instability in gastric cancer.Scientific reports · 2023Article
- Do Elevated YKL-40 Levels Drive the Immunosuppressive Tumor Microenvironment in Colorectal Cancer? Assessment of the Association of the Expression of YKL-40, MMP-8, IL17A, and PD-L1 with Coexisting Type 2 Diabetes, Obesity, and Active Smoking.Current issues in molecular biology · 2023Article
- Bioinformatics analysis of key biomarkers for bladder cancer.Biomedical reports · 2023Article
- A novel humanized Chi3l1 blocking antibody attenuates acetaminophen-induced liver injury in mice.Antibody therapeutics · 2023Article
- Targeting Chitinase 1 and Chitinase 3-Like 1 as Novel Therapeutic Strategy of Pulmonary Fibrosis.Frontiers in pharmacology · 2022Review
- YKL-40 protein expression in human tumor samples and human tumor cell line xenografts: implications for its use in tumor models.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- Structural and kinetic analyses of holothurian sulfated glycans suggest potential treatment for SARS-CoV-2 infection.The Journal of biological chemistry · 2021Article
- Inflammatory Biomarker Score Identifies Patients with Six-Fold Increased Risk of One-Year Mortality after Pancreatic Cancer.Cancers · 2021Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The heparin-binding glycoprotein YKL-40 (CHI3L1) is intimately associated with microvascularization in multiple human diseases including cancer and inflammation. However, the heparin-binding domain(s) pertinent to the angiogenic activity have yet been identified. YKL-40 harbors a consensus heparin-binding motif that consists of positively charged arginine (R) and lysine (K) (RRDK; residues 144-147); but they don't bind to heparin. Intriguingly, we identified a separate KR-rich domain (residues 334-345) that does display strong heparin binding affinity. A short synthetic peptide spanning this KR-rich domain successfully competed with YKL-40 and blocked its ability to bind heparin. Three individual point mutations, where alanine (A) substituted for K or R (K337A, K342A, R344A), led to remarkable decreases in heparin-binding ability and angiogenic activity. In addition, a neutralizing anti-YKL-40 antibody that targets these residues and prevents heparin binding impeded angiogenesis in vitro. MDA-MB-231 breast cancer cells engineered to express ectopic K337A, K342A or R344A mutants displayed reduced tumor development and compromised tumor vessel formation in mice relative to control cells expressing wild-type YKL-40. These data reveal that the KR-rich heparin-binding motif is the functional heparin-binding domain of YKL-40. Our findings shed light on novel molecular mechanisms underlying endothelial cell angiogenesis promoted by YKL-40 in a variety of diseases.
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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.