Database for Annotation, Visualization and Integrated Discovery 2.1
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heparanase 2 (inactive)(HPSE2) heparanase 2 (inactive)(HPSE2) Related Genes Homo sapiens
CHROMOSOME 10,
CYTOBAND 10q23-q24,
ENSEMBL_GENE_ID ENSG00000172987,
GENERIF_SUMMARY Heparanase may facilitate invasion and metastasis of gastric carcinoma cells., Study demonstrating that increased heparanase expression in prostate cancer tissues is due to promoter hypomethylation and up-regulation of transcription factor EGR1., Heparanase expression seems to be involved in the invasiveness and aggressiveness of head and neck squamous cell carcinomas., Heparanase expression is inversely correlated with survival of nasopharyngeal carcinoma (NPC) patients, indicating heparanase is a reliable prognostic factor, and further supports that heparanase is a valid target for the development of anti-cancer drugs., HPSE plays a role in extracellular matrix remodeling and in increasing heparin-binding growth factor release during embryo implantation., Data suggest that loss of modified heparan sulphate in the GBM is mediated by an increased heparanase presence and may play a role in the pathogenesis of diabetes-induced proteinuria., Heparanase 2 is involved in neoplastic proliferation, but it was not exclusively associated with the malignant process., These results indicate a regulatory effect of heparanase on TFPI and TFPI-2 in trophoblasts, suggesting a potential involvement of heparanase in early miscarriages., Results demonstrated that the effectors from heparanase peptide-immunized mice could effectively lyse various tumor cells that were heparanase positive and HLA-A*0201 matched., We now report evidence that Heparanse 2 (HPSE2) is the culprit gene for the syndrome. Mutations with a loss of function in the Heparanase 2 (HPSE2) gene, Homozygous exonic deletions, nonsense mutations, and frameshift mutations in five further unrelated families confirmed HPSE2 as the causative gene for UFS, Studies indicate that cathepsin L as the heparanase activating protease., HPSE2 c.631T>C (p.Y211H) is a novel benign SNP and c.1628A>T (p.N543I) is the disease-causing mutation in urofacial syndrome., A large region of marker homozygosity was observed at 10q24, consistent with known autosomal recessive inheritance, family consanguinity and previous genetic mapping in other families with Ochoa syndrome., Data indicate that the overexpression of HPSE1 and HPSE2 in the intervertebral degenerated discs suggests a role for these factors in mediating extracellular matrix remodeling in degenerative discs during disease development., High expression of heparanase-2 is associated significantly with gastric tumor growth and differentiation, autonomic neural protein implicated in bladder emptying, Heparanase 2 is more intensely expressed in the glandular tissue of cancer than in nonneoplastic endometrium; the HPSE2 expression in the stromal tissue is higher in the nonneoplastic controls compared with cancer mainly in the secretory endometrium., HPSE2 mutations were found in one Urofacial syndrome family but not detected in patients with non-neurogenic neurogenic bladder and severe lower urinary tract dysfunction, Our findings identified these 2 genes as a novel breast cancer biomarker gene set, which may facilitate the diagnosis and treatment in breast cancer clinical therapies.,
OFFICIAL_GENE_SYMBOL HPSE2,
OMIM_DISEASE Urofacial syndrome 1,
SP_COMMENT function:Endoglycosidase which is a cell surface and extracellular matrix-degrading enzyme. Cleaves heparan sulfate proteoglycans (HSPGs) into heparan sulfate side chains and core proteoglycans. Also implicated in the extravasation of leukocytes and tumor cell lines. Due to its contribution to metastasis and angiogenesis, it is considered to be a potential target for anti-cancer therapies., similarity:Belongs to the glycosyl hydrolase 79 family., tissue specificity:Widely expressed, with the highest expression in brain, mammary gland, prostate, small intestine, testis and uterus. Found both in normal and cancer tissues.,
heparanase(HPSE) heparanase(HPSE) Related Genes Homo sapiens
CHROMOSOME 4,
CYTOBAND 4q21.3,
ENSEMBL_GENE_ID ENSG00000173083,
ENTREZ_GENE_ID 10855,
GENERIF_SUMMARY Erythromycin and clarithromycin modulation of growth factor-induced expression of heparanase mRNA on human lung cancer cells in vitro., Activation, processing and trafficking of extracellular heparanase by primary human fibroblasts., REVIEW, Results indicate consistent expression of heparanase in normal and abnormal placenta, in small fetal vessels and in a variety of trophoblast subpopulations with different invasive potentials., It was concluded that heparanase might play an important role in the development of invasion and metastasis of the gastric cancer., Cell surface expression and secretion markedly promote tumor angiogenesis and metastasis., structural recognition plays critical roles in tumor metastasis; specificity of the purified recombinant human heparanase, Heparanase-1 expression is associated with the metastatic potential of breast cancer, Heparanase participates in the structure damage and remodeling of abdominal aorta at matrix level, which contributes to abdominal aortic aneurysm (AAA) formation., reduced heparanase mRNA expression may result in abnormal cell growth and correlate with esophageal squamous cell carcinoma progression, Expression correlates with tumor invasiveness patterns in human oral squamous cell carcinoma xenografts in SCID mice., Intracellular processing of the heparin proteoglycan polysaccharide chains is catalyzed by heparanase., results suggest that the expression of heparanase may influence different malignant behaviors in endometrial cancer, heterodimer formation is necessary and sufficient for heparanase enzymatic activity in mammalian cells, heparanase gene transcription is regulated in activated T cells by early growth response 1, NF-kappaB is an essential factor in the regulatory mechanisms of heparanase gene transcription., glycosylation affected the kinetics of endoplasmic reticulum-to-Golgi transport and of secretion of the enzyme, Heparanase activates signal transduction pathways and, depending on its expression levels, may modulate tumor progression in glioma cells., Increased HPR1 expression is associated with thyroid tumor malignancy and may significantly contribute to thyroid tumor metastases, characterization of the hpa-tg mice emphasizes the involvement of heparanase and heparan sulfate in processes such as embryonic implantation, food consumption, tissue remodeling, and vascularization, Tobacco etch virus protease cleavage sites of heparanase are engineered to provide evidence that proteolytic processing at both junctions between residues 109 and 110 and 157 and 158 leads to activation of the 65 kDa heparanase precursor., Heparanase gene expression may play some roles in the pathogenesis of endometriosis, and it may participate the regulation of menstrual cycle and may be an important target of the trentment for endometriosis., heparanase is translocated into the cell nucleus where it may degrade the nuclear heparan sulfate and thereby affect nuclear functions that are thought to be regulated by heparan sulfate, Heparanase, CD44v6 and nm23 may play important roles in the invasive infiltration and lymph node metastasis in gastric carcinomas., In sites relatively remote from inflammatory foci, within blood vessels and extravascular tissues, heparanase can act as a T cell cytokine that is involved in regulating cell activation and behavior., Inflammatory cytokines and fatty acids regulate endothelial cell heparanase expression., Heparanase mRNA may be important to the loss of glomerular negative charge in GBM and lead to proteinuria in steroid responsive nephrotic syndrome., Heparan sulfate is not only a substrate for, but also a regulator of, heparanase., Point mutation may be one of the causes for enhanced heparanase mRNA expression in hepatocellular carcinoma., one of the roles CREB plays in the acquisition of melanoma cells metastatic phenotype is affecting HPSE-1 activity, Heparanase is a critical determinant of myeloma dissemination and growth in vivo., dysregulated heparanase expression may play a significant role in the pathogenesis of steroid-sensitive nephrotic syndrome, possibly through an abnormality in post-translational control of latent heparanase activation, Expression of heparanase was significantly more frequent in tumors of higher TNM stage, higher Dukes stage, higher vascular infiltration, higher lymph vessel infiltration and poor survival., HPSE-1 likely plays important roles in regulating the in vivo growth and progression of melanoma, Results suggest that proheparanase processing at site 2 is brought about by cathepsin L-like proteases., NF-kappaB RelA (p65) activation was related with increased heparanase gene expression and correlated with poor clinicopathological characteristics in gastric cancers., Heparanase plays a role in ovarian tissue remodeling during folliculogenesis and corpus luteum formation and regression., HPR1 was expressed at a significantly higher frequency in the invasive comedo and DCIS with microinvasion subtypes than in the noninvasive subtypes. HPR1 expression was inversely associated with HS deposition in the extracellular basement membrane., identified three potential heparin binding domains and provided evidence that one of these is mapped at the N terminus of the 50-kDa active heparanase subunit, Loss of heparan sulfsate in the glomerular basement membrane in diabetic nephropathy is attributable to accelerated heparan sulfate degradation by increased HPR1 expression., expression during the pathogenesis of bladder cancer is due to promoter hypomethylation and transcription factor EGR1, EGR1 regulates heparanase transcription in tumor cells and importantly, can have a repressive or activating role depending on the tumor type, The expression of heparanase mRNA in an esophageal cancer cell line can be inhibited by antisense oligonucleotides, which can inhibit metastasis of esophageal squamous cell carcinoma or other tumors by inhibiting the expression of heparanase., In summary, we have characterized a link between leukomogenic factors and the downregulation of heparanase in myeloid leukemic cells., results emphasize the significance and clarify the involvement of heparanase in primary breast cancer progression by generating a supportive microenvironment that promotes tumor growth, angiogenesis and survival, Brain-metastatic melanoma cells (B16B15b) showed augmenting levels of HPSE-1 protein expression in a time-dependent manner. Secondly, B16B15b cells pre-treated with HPSE-1 showed a significant increase in the number of cells that invaded into the brain ., heparanase may play a novel role for cyclooxygenase 2 mediated tumor angiogenesis in breast-cancer progression, HPSE-1 activity may represent a physiological mechanism involved in neural cellular differentiation, proteoglycans tonically suppress osteoblast function and that this inhibition is alleviated by heparan sulfate degradation with heparanase, Heparanase is a key enzyme in dendritic cell transmigration through the extracellular matrix., Hypoxia plays an important role in the augmentation of the heparanase expression and the invasiveness of human laryngeal carcinomas., Heparanase resides in and accumulates in the lysosomal compartment, where it may participate in normal turnover of heparan sulfate. The secreted enzyme facilitates cell invasion associated with cancer metastasis, angiogenesis, and inflammation., Expressions of p75(NTR) and HPSE-1 correlated with each other in medulloblastoma., REVIEW of heparanase involvement in cancer metastasis and angiogenesis, heparanase modifies FGF2 binding, signaling, and angiogenesis in metastatic melanoma cells, This hypothesis indicates a possible novel function of heparanase and its link to HIF1alpha and Cox-2, and therefore this function would give us a clue about potential new strategies for cancer therapy., HPSE 'off/on switch', HPSE is involved in the pathogenesis of proteinuria in overt diabetic nephropathy by degradation of heparan sulfates, 4 Israeli Jewish populations (Ashkenazi, North African, Mediterranean and Near Eastern) were examined for 7 HPSE gene SNPs. Four out of 7 SNPs (rs4693608, db11099592, rs4364254, db6856901) were found to be polymorphic., The higher expression of Hpa and Ang-2 in ectopic and eutopic endometrium may play an important role in the pathogenesis and development of endometriosis., Splice 5 escaped proteolytic cleavage, was devoid of HS degradation activity and exhibited diffused rather than granular cellular localization., Nuclear localization of heparanase predicts a favorable outcome in patients with squamous cell carcinoma of the head and neck., heparanase-1 expression and heparan sulphate proteoglycan degradation are induced by estradiol in human endometrium, we speculate that nuclear translocation of enzymatically active heparanase may be involved in cellular differentiation., Heparanase influences expression and shedding of syndecan-1, The CGC HSPE-1 haplotype associates with stage in ovarian cancer. This haplotype may affect splicing of the HSPE-1 gene, as in silico it alters the presence of a splicing motif., The combined effects of heparanase and HSULF could account for the lack of biologically active HS in tumour cells rather than deficiencies in the biosynthetic enzymes., Genetic downregulation of the expression of heparanase may serve as an efficient cancer therapeutic for human HCC., There is no significant difference in heparanase-1 expression in the eutopic endometrium from women with or without endometriosis., This review focuses on the role of heparanase in heparan sulfate degradation in proteinuric diseases and the possibility/feasibility of heparanase inhibitors, High expression of heparanase, combined with NF-kappaB p65, may contribute to the highly invasive and metastatic behavior of gallbladder carcinoma., certain HPSE gene SNPs may contribute to basal heparanase gene expression; alterations in this gene are an important determinant in the pathogenesis of ALL, AML and MM, Heparanase induction by estrogen receptors represents an important pathway in breast tumorigenesis and may be responsib, for failure of tamoxifen therapy in some patients., Heparanase and NF-kappaB p65 proteins were found in 30 (62.5%) and 22 (45.9%) tumor specimens, respectively, a rate significantly higher than that in the adjacent tissues., HPSE plays a role in extracellular matrix remodeling and in increasing heparin-binding growth factor release during embryo implantation., Heparanase pro-enzyme reverses the anti-coagulant activity of unfractionated heparin on the coagulation pathway and on thrombin activity. Heparanase pro-enzyme abrogated the factor X inhibitory activity of low-molecular-weight heparin (LMWH)., Accumulating evidence suggests that small inhibitory genetic molecules targeting heparanase are of value for control and treatment of human malignancies., Heparanase directly contributes to prostate tumor growth in bone and its ability to metastasize to distant organs., Heparanase facilitates blood coagulation by dissociation of TFPI from the vascular surface shortly after local elevation of heparanase levels, and subsequent induction of TF expression., The high expression of HPA mRNA and HIF-1alpha protein is correlated with carcinogenesis, progression, invasion and metastasis of esophageal squamous cell carcinoma., The coexpression of heparanase and vascular endothelial growth factor in atypical melanocytes and melanoma cells suggests their function in cell migration and invasion., Trophoblast heparanase is not required for invasion in vitro. Its abundant expression suggests another role during pregnancy, perhaps in controlling the availability of ECM-bound growth factors or acting as a transcription factor., The expression of HPSE is significantly increased in squamous carcinomas of head and neck, and is directly related to the clinical stage and lymph node metastasis., Hpa may up-regulate the expression of C-erbB-2 in invasive ductal breast carcinoma., Cathepsin L has a role in processing and activation of proheparanase through multiple cleavages of a linker segment, heparanase overexpression can facilitate tumor invasion and accelerate bone destruction caused by prostate cancer bone metastasis., Heparanase (HPSE) activity was dramatically higher in Synovial fluid (SF) and Synovial tissue (ST)of rheumatoid arthritis (RA) patients than in SF and ST from Osteoarthritis patients and asymptomatic donors;HPSE RNA was upregulated in ST of RA patients, pro-adhesive properties of heparanase are mediated by its interaction with cell surface HS proteoglycans, and utilized the KKDC peptide to examine this possibility, Heparanase 1 is a key actor of inner root sheath differentiation and hair homeostasis., Strong heparanase expression is related with the degradation of basement membrane which allows or accelerates tumor invasion and metastasis., findings suggest that heparanase expression and cellular localization are decisive for lung cancer patients' prognosis, most likely because of heparanase-mediated tumor cell dissemination by blood and lymph vessels., Overexpressed heparanase and its splice variant localize to the endoplasmic reticulum independent of glycosylation in COS-7 cells., Results indicate that heparanase has pleiotropic effects on tumor cells., The hydrophobic C-terminus region of heparanase is a determinant for its intracellular trafficking to the Golgi apparatus, followed by secretion, activation, and tumor cell migration., Heparanase seems to be significantly associated with lymph node metastasis as well as dedifferentiation. We assume that HPSE plays a crucial role for the aggressiveness of pancreatic cancer., The overexpression of heparanase may play an important role in hepatocarcinogenesis, progression, and metastases of hepatocellular carcinoma., heparanase plays a unique dual role in tumor metastasis, facilitating tumor cell invasiveness and inducing VEGF C expression, thereby increasing the density of lymphatic vessels that mobilize metastatic cells, heparanase plays an important role in invasion and metastasis in renal cell carcinoma, heparanase acts as a master regulator of the aggressive tumor phenotype by up-regulating protease expression and activity within the tumor microenvironment, role for heparanase in the regulation of arterial structure, mechanics, and repair, The expression of heparanase was associated with invasion, metastasis and prognosis of nasopharyngeal cancer., Hypoxia promotes the expression of HPA and the invasiveness of SKOV3 cells through the HIF-1alpha pathway., Results show that heparanase alters the level of nuclear syndecan-1., mRNA and protein are detected in inflammatory sinus mucosa and nasal polyps but not in normal sinus mucosa, The current study indicates that rs4693608 and rs4364254 SNPs are involved in the regulation of heparanase expression and provides the basis for further studies on the association between HPSE gene SNPs and disease outcome., Changes in plasma HP levels correlated with response to treatment for children diagnosed with Hodgkin lymphoma, The expressions of HGF and Hpa in laryngeal squamous cell carcinoma are higher than that in nonmalignant tissues, and correlate with lymph node metastasis, clinical stages and pathological grading., HPSE gene expression is involved in rhabdomyosarcoma tumor invasion., Heparanase expression is already induced in Barrett's epithelium without dysplasia, and is further increased during progression through distinct pathological stages, namely, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma., syndecan-1 and FGF-2, but not FGFR-1 share a common transport route and co-localize with heparanase in the nucleus, and this transport is mediated by the RMKKK motif in syndecan-1, Glioma tissues contain increased levels of heparanase, heparanase has a role in invasiveness, metastasis and angiogenesis, but not proliferation of human gastric cancer cells, The gene expression of heparanase in cervical cancer enhances growth, invasion, and angiogenesis of the tumor., up-regulation of Hpa by hypoxia is NF-kappaB-dependent in MIA PaCa-2 cells, T5 is a novel functional splice variant of human heparanase endowed with protumorigenic characteristics, The present study indicates a highly significant correlation of HPSE gene single-nucleotide polymorphisms rs4693608 and rs4364254 and their combination with the risk of developing acute graft-versus-host disease., pathway driven by heparanase expression in myeloma cells, Altogether, these findings support the notion that HPSE is a critical downstream target of HER2 mechanisms driving BMBC and is potentially relevant for BMBC therapeutic interventions., Decreased expression of Syndecan-1 mRNA and the increased expression of HPA-1 mRNA can promote the invasion and metastasis of colorectal cancer., HPSE expresses and functions in human osteoblasts. It may mediate osteoblastogenesis through regulation of osteogenic gene expression and histone H3 modification., may facilitate the function of heparan sulfate-binding growth factors that elicit an angiogenic response and favor osteoclastogenesis in ameloblastomas, HPSE, HIF-1alpha and VEGF play a role in tumor angiogenesis and promote malignant progress of retinoblastoma., results indicate that aberrant expression of EGR1 in gastric cancer is associated with tumor invasion and metastasis, and heparanase transcription, The results support the notion that heparanase is a modulator of blood coagulation, and suggest a novel mechanism by which heparanase regulates tissue factor and TFPI levels in endothelial and cancer cells., Single nucleotide polymorphisms of the HPSE gene is associated with gastric cancer., Recent progress in heparanase research emphasizing the molecular mechanisms that govern its pro-tumorigenic and pro-adhesive properties., heparanase is a potential modulator of blood hemostasis, and suggest a novel mechanism by which heparanase increases the generation of activated factor X in the presence of tissue factor and activated factor VII., Preferential up-regulation of heparanase and cyclooxygenase-2 in carcinogenesis of Barrett's oesophagus and intestinal-type gastric carcinoma., Serum heparanase and vascular endothelial growth factor were identified as independent predictive factors for hepatocellular carcinoma, The results suggest that loss of the adenine (A)/uracil (U)-rich consensus element is an important regulatory mechanism contributing to heparanase induction in human cancer., Heparanase expression is induced in Ewing's sarcoma., Data show that BRAF knockdown led to suppression of the expression of the GABPbeta, which involved in regulating HPR1 promoter activity., a novel mechanism driving the HGF pathway whereby heparanase stimulates an increase in both HGF expression and syndecan-1 shedding to enhance HGF signaling., Heparanase expression was found to be insignificant among the various stages in the endometrial pathway to cancer., SST0001, a chemically modified heparin, inhibits myeloma growth and angiogenesis via disruption of the heparanase/syndecan-1 axis, Heparanase levels are elevated in the urine and plasma of type 2 diabetes patients and associate with blood glucose levels., Overexpression of heparanase influenced expression of most genes involved in heparan sulfate proteoglycan biosynthesis, albeit to a different degree in the cortex and thalamus of the transgenic mice., findings uncover a new level of regulation governing sVEGF-R1 retention versus release and suggest that manipulations of the heparin/heparanase system could be harnessed for reducing unwarranted release of sVEGF-R1 in pathologies such as preeclampsia, HPR1 production is increased in endothelial cells from rat models of diabetes, and in macrophages in atherosclerotic lesions of diabetic and nondiabetic patients. Increased HPR1 production may contribute to pathogenesis and progression of atherosclerosis., Advanced glycation end-products induce heparanase expression in endothelial cells, Heparanase expression was present in 57 (67.8%) of the 84 endometrial carcinomas, and was significantly associated with the endometrioid histotype, Over-expression of heparanase demonstrates the importance of heparan sulfate proteoglycans for the uptake of intestinal derived lipoproteins and its role in the formation of fatty streaks, heparanase generates a vicious cycle that powers colitis and the associated tumorigenesis, Multiple antigenic peptides of human heparanase elicit a much more potent immune response against tumors, analyzed the involvement of heparanase, a heparan sulfate glycosidase, in the homeostasis of proximal tubular epithelial cells in the diabetic milieu, Targeted silencing of heparanase gene by siRNA could dramatically inhibit the invasiveness and metastasis of osteosarcoma cells., Study found positive staining for HPA-1 in 15% of adrenocortical adenomas and 91.67% of human adrenocortical carcinomas., Heparanase-mediated loss of nuclear syndecan-1 enhances histone acetyltransferase (HAT) activity to promote expression of genes that drive an aggressive tumor phenotype, Molecular model of human heparanase with proposed binding mode of a heparan sulfate oligosaccharide and catalytic amino acids., Elevated serum CL, Hpa, and MMP-9 levels are correlated with malignant invasion and progression in ovarian cancer., heparanase expression is associated with histone modifications and promoter DNA methylation plays a role in the control of gene silencing in glioblastoma, Hyperpigmentation in human solar lentigo is promoted by heparanase-induced loss of heparan sulfate chains at the dermal-epidermal junction., heparanase enhances pituitary cell viability and proliferation and may thus contribute to pituitary tumor development and progression., Findings indicate the prominent presence of heparanase in the epithelial component of radicular cysts versus sparse or no expression in periapical granulomas., Heparanase and syndecan-1 interplay orchestrates fibroblast growth factor-2-induced epithelial-mesenchymal transition in renal tubular cells., heparanase over-expression is associated with clear cell renal cell cancer., Heparanase enhances the phosphorylation of STAT3 and STAT5b but not STAT5a in head and neck cancers., study demonstrates a role for heparanase in modulation of acute localized inflammation and mast cell activity, accordingly affecting inflammatory pain, Heparanase can induce angiogenesis to promote tumor growth by releasing bFGF and VEGF in nasopharyngeal angiofibroma., SNPs in HPSE play an important role in gastric cancer progression and survival, and perhaps may be a molecular marker for prognosis and treatment values., Role for heparanase in sustaining immune cell-epithelial crosstalk that underlies intestinal inflammation and the associated cancer. Review., These results suggest that small RNAs targeting transcription start site can induce transcriptional gene silencing of heparanase via interference with transcription initiation., the expression levels of HPSE and miR-1258 in NSCLC tissue are closely related. In HPSE-positive samples, the expression levels of miR-1258 were relatively low; in HPSE-negative samples, the expression levels of miR-1258 were relatively high., Heparanase and COX-2 might play complementary roles in the stepwise progression of oral epithelial dysplasia to carcinoma., Taking into account the pro-metastatic and pro-angiogenic functions of heparanase, with over-expression in human malignancies and abundance in platelets and placenta., data indicate that intact heparan sulfate chains are required to mediate neuroinflammatory responses, and point to heparanase as a modulator of this process, with potential implications for Alzheimer's disease, demonstrated that artificial miRNAs against HPSE might serve as an alterative mean of therapy to low HPSE expression and to block the adhesion, invasion, and metastasis of melanoma cells, The results in this study demonstrate that genetic alteration and reduction of HPSE expression are associated with tumor progression and poor prognosis of hepatocellular carcinoma., Heparanase is upregulated and associated with the VEGF expression in hypoxia-induced retinal diseases., Elevated urine heparanase levels are associated with proteinuria and decreased renal allograft function., Heparanase enhances the insulin receptor signaling pathway to activate extracellular signal-regulated kinase in multiple myeloma, Heparanase activates macrophages, resulting in marked induction of cytokine expression associated with plaque progression toward vulnerability., heparanase plays essential roles in regulating the invasion, proliferation, and angiogenesis of A549 cells, T5, a novel splice variant of heparanase, is a functional, pro-tumorigenic entity., These results suggest that heparanase participates in tumor growth of cervical cancer by influencing the proliferation and apoptosis of cervical cancer cells, study did not find any significant difference in heparanase promoter methylation between colon carcinoma and normal colonic mucosa, suggesting that heparanase overexpression in colon carcinoma is mediated by other mechanisms, Data indicate that the overexpression of HPSE1 and HPSE2 in the intervertebral degenerated discs suggests a role for these factors in mediating extracellular matrix remodeling in degenerative discs during disease development., MiR-1258 may play an important role in breast cancer development and progression by regulating the expression of HPSE, and they might be potential prognostic biomarkers for breast cancer., Heparanase regulates secretion, composition, and function of tumor cell-derived exosomes, The activation of endoplasmic reticulum stress is involved in the enhanced invasion and migration ability of breast cancer cells and this effect is associated with the activation of heparanase., Heparanase is critically involeved in inflammation, diabetes mellitus and atherosclerosis. (Review), Heparanase mediates unexpected intracellular effects on T cell differentiation and insulin-producing beta cell survival in T cell-dependent autoimmune Type 1 diabetes mellitus. (Review), Induction of heparanase prior to the appearance of malignancy was reported in essentially all inflammatory conditions. (Review), The plastic substrate specificity suggests a complex role of heparanase in regulating the structures of heparan sulfate in matrix biology. (Review), Heparanase is up-regulated in atherosclerosis and other vessel wall pathologies. (Review), Targeting of heparanase-modified syndecan-1 by prosecretory mitogen lacritin requires conserved core GAGAL plus heparan and chondroitin sulfate as a novel hybrid binding site that enhances selectivity., Characterization of heparanase-induced phosphatidylinositol 3-kinase-AKT activation and its integrin dependence., Elevation of serum heparanase is associated with Crohn's disease., CCL19/CCR7 may upregulate the expression of heparanase via Sp1 and contribute to the invasion of A549 cells., The prognostic role of FLT1/VEGFR1, heparanase and epidermal growth factor receptor gene expression in patients with resected cholangiocarcinoma, was investigated., The relative Heparanase mRNA expression level in hepatocellular carcinoma was lower than that in noncancerous tissue., Heparanase is frequently expressed in oral mucosal melanoma., The study suggest that one of the causes of unexplained miscarriages may result from the impaired expression of heparanase and heparin-binding EGF-like growth factor., role of HPSE in tumor invasion and metastasis in ovarian cancer and concluded that either the expression of HPSE in cancer and/or the serum concentration of HPSE may be a useful biomarker for the evaluation of surgery effects and prognosis prediction., the function of heparan sulfate proteoglycans and heparanase in breast cancer behavior and progression, is discussed., Involvement of heparanase in the pathogenesis of psoriasis and a role for the enzyme in facilitating abnormal interactions between immune and epithelial cell subsets of the affected skin., results revealed that dialysis treatments induce change in the transcriptomic pattern of biosynthetic proteoglycans in PBMCs with an up-regulation of HPSE., HPV16 oncogene E6 is capable of inducing overexpression of heparanase in head and neck squamous cell carcinoma., this study describes (1)H NMR spectroscopic studies of the hydrolysis of the pentasaccharide substrate fondaparinux by heparanase, and provide conclusive evidence that heparanase hydrolyses its substrate with retention of configuration and is thus established as a retaining glycosidase, the importance of rs4693608 SNP for HPSE gene expression in activated MNCs, indicating a role in allogeneic stem cell transplantation, including postconditioning, engraftment, and GVHD., Heparanase potentiates the bioactivity of resistin in its standard bioassay., DNA methylation play the regulation role in heparanase gene in different stages of breast cancer, We found that heparanase induction is associated with decreased levels of CXCL10, suggesting that this chemokine exerts tumor-suppressor properties in myeloma., Together, these data indicate a role for heparanase in inflammatory cell trafficking in vivo that appears to require enzymatic activity., Heparanase was localized to the cytoplasm and nucleus of tumor cells and to cells within the microenvironment in different types of lung cancer., Because HS with unsubstituted glucosamine residues accumulates in heparanase-expressing breast cancer cells, we assumed that these HS structures are resistant to heparanase and can therefore be utilized as a heparanase inhibitor., High heparanase expression is associated with oral squamous cell carcinoma., serum levels of HPSE were significantly higher in breast cancer patients than in benign breast disease and in healthy controls., Taking into account the prometastatic, pro-angiogenic and pro-coagulant functions of heparanase, over-expression in human malignancies and abundance in platelets, implies that heparanase is potentially a good target for cancer therapy., No correlation was observed between heparanase staining and soft tissue sarcoma tumor aggressiveness, tumor recurrence or patient survival., Overexpression of Heparanase is associated with lymph node metastasis in large, high-grade breast tumors., The aim of this study was to investigate whether HPSE can modulate the expression and the effects of TGF-beta in tubular cells., Polymorphisms in the heparanase gene in multiple myeloma association with bone morbidity and survival, Elevated heparanase procoagulant activity in patients with lung cancer reveals a new mechanism of coagulation system activation in malignancy. Heparanase procoagulant activity can potentially be used as a predictor for survival., Increased upstream stimulatory factor in HCC is associated with heparanase expression. USF might be an important factor in regulating HPSE expression and act as a novel marker of metastatic recurrence of HCC patients, High heparanase expression is associated with hepatoma., Heparanase is over expressed in preeclamptic placentas compared to normal healthy controls, suggesting its role in the development of preeclampsia., Suggest that heparanase facilitates invasion and migration of human gastric cancer cells probably through elevating phosphorylation of Src and p38., Increased expression of beta-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 is significantly correlated with decreased survival and poor prognosis in acral melanoma., The close correlation between heparanase and COX-2 expression in lymphangiogenesis of cervical cancer., Heparanase 1 is more intensely expressed in the glandular tissue of high-grade compared with type I endometrial carcinomas., heparin and VEGF did not influence HPSE-expression. The presumed pregnancy-protecting effects of heparin may partially be due to an increase of trophoblast proliferation and not via regulation of HPSE expression., Overexpression of heparanase lowers the amyloid burden in amyloid-beta precursor protein transgenic mice, our results suggest that HPSE contributes to the proliferation and metastasis of Ovarian cancer and HPSE might be a potent molecular target for Ovarian cancer treatment, miRNA-558 promotes tumorigenesis and aggressiveness of neuroblastoma cells through activating the transcription of heparanase, Since blockade of heparanase by LMWH has functional consequences for reduced VLA-4 binding, latent heparanase appears as a novel, so far unnoticed target of heparin, underlying its antimetastatic activity., upregulation of heparanase expression via the PI3K/Akt/NF-kappaB signaling pathway is associated with gastric cancer metastasis., our findings identify heparanase as a modulator of the syndecan-syntenin-ALIX pathway, fostering endosomal membrane budding and the biogenesis of exosomes by trimming the heparan sulfate chains on syndecans, Heparanase procoagulant activity was significantly higher in shift work nurses compared to daytime work nurses., Findings identify a dual function for HPSE in malignant melanoma with a protumorigenic extracellular activity and a tumor-suppressive nuclear action., HPSE deficiency in in vitro-engineered and cultured tumor-specific LTE-T cells may limit their antitumor activity in stroma-rich solid tumors, upregulated through NF-kB and translocated to the cell surface upon herpes simplex virus-1 infection for the removal of heparan sulfate to facilitate viral release, Report FGF23/klotho/heparanase signaling axis active in multiple myeloma., heparanase contributes to allergen-induced eosinophil recruitment to the lung., Heparanase resides within autophagosomes. Heparanase-overexpressing cells were more resistant to stress and chemotherapy in a manner associated with increased autophagy., JAK-2 V617F mutation results in heparanase up-regulation via the erythropoietin receptor., Studies indicate that heparanase (HPSE) has been a potential target of medical treatment., The authors present crystal structures of human HPSE at 1.6-A to 1.9-A resolution that reveal how an endo-acting binding cleft is exposed by proteolytic activation of latent proHPSE., Taken together, it is concluded that colon 26 cells transduce the heparanase-mediated signal through heparan sulfate binding., Our findings suggest a link between heparanase, syndecan-1, and VEGF in the progression of PDR and that heparanase is a potential target for therapy of diabetic retinopathy., higher heparanase expression in gastric cancer is associated with clinicopathologic features of depth of invasion, lymph node metastasis.,
OFFICIAL_GENE_SYMBOL HPSE,
SP_COMMENT enzyme regulation:Inhibited by EDTA, laminarin sulfate and, to a lower extent, by heparin and sulfamin and activated by calcium and magnesium., function:Endoglycosidase which is a cell surface and extracellular matrix-degrading enzyme. Cleaves heparan sulfate proteoglycans (HSPGs) into heparan sulfate side chains and core proteoglycans. Also implicated in the extravasation of leukocytes and tumor cell lines. Due to its contribution to metastasis and angiogenesis, it is considered to be a potential target for anti-cancer therapies., PTM:N-glycosylated. Glycosylation of the 50 kDa subunit appears to be essential for its solubility., PTM:Proteolytically processed. The cleavage of the 65 kDa form leads to the generation of a linker peptide, 8 kDa and 50 kDa product. The active form, the 8/50 kDa heterodimer, is resistant to degradation. Complete removal of the linker peptide appears to be a prerequisite to the complete activation of the enzyme., similarity:Belongs to the glycosyl hydrolase 79 family., subcellular location:Secreted, internalised and transferred to late endosomes/lysosomes as a proheparanase. In lysosomes, it is processed into the active form, the heparanase. The uptake or internalisation of proheparanase is mediated by HSPGs. Heparin appears to be a competitor and retain proheparanase in the extracellular medium., subunit:The active heterodimer is composed of the 8 and 50 kDa subunits, the proteolytic products., tissue specificity:Highly expressed in placenta and spleen and weakly expressed in lymph node, thymus, peripheral blood leukocytes, bone marrow, endothelial cells, fetal liver and tumor tissues.,