ArticleOncogene2015
Nuclear heparanase-1 activity suppresses melanoma progression via its DNA-binding affinity.
Article in Oncogene, 2015. 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
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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
30 citing papers in PubMed, 47 citations in OpenAlex.
- Preparation, characterization and anticancer applications of HAase from Pedobacter heparinus.BMC cancer · 2026Article
- Heparan Sulfate Proteoglycans (HSPGs) and Their Degradation in Health and Disease.Biomolecules · 2025Review
- The Pathophysiological Functions of Heparanases: From Evolution, Structural and Tissue-Specific Perspectives.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Article
- Identification of biomarkers and potential drug targets for esophageal cancer: a Mendelian randomization study.Scientific reports · 2025Article
- Extracellular matrix in skin diseases: The road to new therapies.Journal of advanced research · 2023Review
- Heparanase-A single protein with multiple enzymatic and nonenzymatic functions.Proteoglycan research · 2023Review
- Regulation of FGF-2, FGF-18 and Transcription Factor Activity by Perlecan in the Maturational Development of Transitional Rudiment and Growth Plate Cartilages and in the Maintenance of Permanent Cartilage Homeostasis.International journal of molecular sciences · 2022Review
- Histone H4 induces heparan sulfate degradation by activating heparanase in chlorine gas-induced acute respiratory distress syndrome.Respiratory research · 2022Article
- Heparanase in cancer progression: Structure, substrate recognition and therapeutic potential.Frontiers in chemistry · 2022Review
- The Heparanase Regulatory Network in Health and Disease.International journal of molecular sciences · 2021Review
- Phenotypic diversity and metabolic specialization of renal endothelial cells.Nature reviews. Nephrology · 2021Review
- Melanoma Associated Chitinase 3-Like 1 Promoted Endothelial Cell Activation and Immune Cell Recruitment.International journal of molecular sciences · 2021Article
- Disruption of innate defense responses by endoglycosidase HPSE promotes cell survival.JCI insight · 2021Article
- Biology of the Heparanase-Heparan Sulfate Axis and Its Role in Disease Pathogenesis.Seminars in thrombosis and hemostasis · 2021Review
- Dissociation of DNA damage sensing by endoglycosidase HPSE.iScience · 2021Article
- Heparan Sulfate Glycosaminoglycans: (Un)Expected Allies in Cancer Clinical Management.Biomolecules · 2021Review
- Differences of the tumour cell glycocalyx affect binding of capsaicin-loaded chitosan nanocapsules.Scientific reports · 2020Article
- Antiviral Strategies of Chinese Herbal Medicine Against PRRSV Infection.Frontiers in microbiology · 2020Review
- Transcriptomic analysis reveals cell apoptotic signature modified by heparanase in melanoma cells.Journal of cellular and molecular medicine · 2019Article
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 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heparanase-1 (HPSE) plays a pivotal role in structural remodeling of the ECM and the glycocalyx, thus conferring protumorigenic, proangiogenic and prometastatic properties to many cancer entities. In addition to its extracellular function, recent studies suggest an intracellular activity of HPSE with a largely unknown significance during tumor progression. Therefore, we investigated the relevance of the dual functions of HPSE to malignant melanoma in vitro, as well as in different mouse melanoma models based on the intradermal or intravenous injection of melanoma cells. Consistent with its extracellular action, an HPSE deficiency led to a reduced shedding of the glycocalyx accompanied by a reduced availability of vascular endothelial growth factor, affecting tumor growth and vascularization. In contrast, we measured an elevated expression of the protumorigenic factors pentraxin-3, tissue factor, TNF-α and most prominently, MMP-9, upon HPSE knockdown. In vivo, an HPSE deficiency was related to increased lymph node metastasis. Since the inhibition of its extracellular function with heparin was unable to block the gene regulatory impact of HPSE, we proposed an intracellular mechanism. Immunostaining revealed a counter-staining of HPSE and NF-κB in the nucleus, suggesting a close relationship between both proteins. This finding was further supported by the discovery of a direct charge-driven molecular interaction between HPSE and DNA by using atomic force microscopy and a co-precipitation approach. Our findings are novel and point towards a dual function for HPSE in malignant melanoma with a protumorigenic extracellular activity and a tumor-suppressive nuclear action. The identification of molecular strategies to shuttle extracellular HPSE into the nuclei of cancer cells could provide new therapeutic options.
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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.