ArticleOncogene2003
Role of promoter methylation in regulation of the mammalian heparanase gene.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 102 citations in OpenAlex.
- Auranofin Suppresses Cancer Cell Invasion by Inhibiting Heparanase-1 Expression via the aPKC-NF-κB Pathway.International journal of molecular sciences · 2026Article
- Heparan Sulfate Proteoglycans (HSPGs) and Their Degradation in Health and Disease.Biomolecules · 2025Review
- Structure and Function of the Extracellular Matrix in Normal and Pathological Conditions: Looking at the Bicuspid Aortic Valve.International journal of molecular sciences · 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
- Design of Paromomycin and Neomycin as Sulfated and Hydrophobic Glycans to Target Heparanase-Driven Tumor Progression and Metastasis.Journal of medicinal chemistry · 2025Article
- Heparanase-A single protein with multiple enzymatic and nonenzymatic functions.Proteoglycan research · 2023Review
- The Heparanase Regulatory Network in Health and Disease.International journal of molecular sciences · 2021Review
- 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
- The Structure and Function of the Glycocalyx and Its Connection With Blood-Brain Barrier.Frontiers in cellular neuroscience · 2021Review
- Endothelial glycocalyx as an important factor in composition of blood-brain barrier.CNS neuroscience & therapeutics · 2021Review
- Chemoradiotherapy Increases Intratumor Heterogeneity of HPSE Expression in the Relapsed Glioblastoma Tumors.International journal of molecular sciences · 2020Article
- Forty Years of Basic and Translational Heparanase Research.Advances in experimental medicine and biology · 2020Review
- Transcriptomic analysis reveals cell apoptotic signature modified by heparanase in melanoma cells.Journal of cellular and molecular medicine · 2019Article
- Targeting Heparanase in Cancer: Inhibition by Synthetic, Chemically Modified, and Natural Compounds.iScience · 2019Review
- Methyl donor S-adenosylmethionine (SAM) supplementation attenuates breast cancer growth, invasion, and metastasisOncotarget · 2018Article
- Sulfotransferase and Heparanase: Remodeling Engines in Promoting Virus Infection and Disease Development.Frontiers in pharmacology · 2018Review
- S-adenosyl-methionine (SAM) alters the transcriptome and methylome and specifically blocks growth and invasiveness of liver cancer cells.Oncotarget · 2017Article
- Heparanase: From basic research to therapeutic applications in cancer and inflammation.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2016Review
- Heparanase-neutralizing antibodies attenuate lymphoma tumor growth and metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Mammalian heparanase (endo-beta-glucuronidase) degrades heparan sulfate proteoglycans and is an important modulator of the extracellular matrix and associated factors. The enzyme is preferentially expressed in neoplastic tissues and contributes to tumour metastasis and angiogenesis. To investigate the epigenetic regulation of the heparanase locus, methylation-specific and bisulfite PCR were performed on a panel of 22 human cancer cell lines. Cytosine methylation of the heparanase promoter was associated with inactivation of the affected allele. Despite lack of sequence homology, extensively methylated CpG islands were found both in human choriocarcinoma (JAR) and rat glioma (C-6) cells which lack heparanase activity. Treatment of these cells with demethylating agents (5-azacytidine, 5-aza-2'-deoxycytidine) resulted in stable dose- and time-dependant promoter hypomethylation accompanied by reappearance of heparanase mRNA, protein and enzymatic activity. An inhibitor of histone deacetylase, Trichostatin A, failed to induce either of these effects. Upregulation of heparanase expression and activity by demethylating drugs was associated with a marked increase in lung colonization by pretreated C-6 rat glioma cells. The increased metastatic potential in vivo was inhibited in mice treated with laminaran sulfate, a potent inhibitor of heparanase activity. We propose a model wherein expression of mammalian heparanase gene is modulated by the interplay between trans-activating genetic and cis-inhibitory epigenetic elements in its promoter.
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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.