ArticleCancer cell2012
Targeted disruption of heparan sulfate interaction with hepatocyte and vascular endothelial growth factors blocks normal and oncogenic signaling.
Article in Cancer cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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
24 citing papers in PubMed, 44 citations in OpenAlex.
- Article
- Chemistry and Function of Glycosaminoglycans in the Nervous System.Advances in neurobiology · 2023Review
- N-Glycans in Immortalized Mesenchymal Stromal Cell-Derived Extracellular Vesicles Are Critical for EV-Cell Interaction and Functional Activation of Endothelial Cells.International journal of molecular sciences · 2022Article
- Suppression of heparan sulfation re-sensitizes YAP1-driven melanoma to MAPK pathway inhibitors.Oncogene · 2022Article
- In-Depth Matrisome and Glycoproteomic Analysis of Human Brain Glioblastoma Versus Control Tissue.Molecular & cellular proteomics : MCP · 2022Article
- Article
- What Are the Potential Roles of Nuclear Perlecan and Other Heparan Sulphate Proteoglycans in the Normal and Malignant Phenotype.International journal of molecular sciences · 2021Review
- Review
- Heparan Sulfate Synthesized byMolecular cancer research : MCR · 2021Article
- A potential target for liver cancer management, lysophosphatidic acid receptor 6 (LPAR6), is transcriptionally up-regulated by the NCOA3 coactivator.The Journal of biological chemistry · 2020Article
- Heparin Binding Proteins as Therapeutic Target: An Historical Account and Current Trends.Medicines (Basel, Switzerland) · 2019Review
- Feedback regulation of RTK signaling in development.Developmental biology · 2019Review
- The neutralization of heparan sulfate by heparin-binding copolymer as a potential therapeutic target.RSC advances · 2019Article
- Extracellular Matrix Influencing HGF/c-MET Signaling Pathway: Impact on Cancer Progression.International journal of molecular sciences · 2018Review
- Article
- MET Inhibition in Clear Cell Renal Cell Carcinoma.Journal of Cancer · 2016Article
- Expression array analysis of the hepatocyte growth factor invasive program.Clinical & experimental metastasis · 2015Article
- Glycosylation in cancer: mechanisms and clinical implications.Nature reviews. Cancer · 2015Review
- Tissue-Specific Gain of RTK Signalling Uncovers Selective Cell Vulnerability during Embryogenesis.PLoS genetics · 2015Article
- Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Hepatocyte growth factor (HGF) and vascular endothelial cell growth factor (VEGF) regulate normal development and homeostasis and drive disease progression in many forms of cancer. Both proteins signal by binding to receptor tyrosine kinases and heparan sulfate (HS) proteoglycans on target cell surfaces. Basic residues comprising the primary HS binding sites on HGF and VEGF provide similar surface charge distributions without underlying structural similarity. Combining three acidic amino acid substitutions in these sites in the HGF isoform NK1 or the VEGF isoform VEGF165 transformed each into potent, selective competitive antagonists of their respective normal and oncogenic signaling pathways. Our findings illustrate the importance of HS in growth factor driven cancer progression and reveal an efficient strategy for therapeutic antagonist development.
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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.