ArticleCell death discovery2021
Heparanase induces necroptosis of microvascular endothelial cells to promote the metastasis of hepatocellular carcinoma.
Article in Cell death discovery, 2021. 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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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Heparanase gene deficiency suppresses atherosclerosis progression and enhances plaque stability in apolipoprotein E gene knockout mice with diabetes.Clinical science (London, England : 1979) · 2026Article
- Angiocrine factors in tumor microenvironment: bidirectional crosstalk, mechanistic insights, and therapeutic strategies.Journal of translational medicine · 2026Review
- Spatial transcriptomic-metabolic features of tumor foci and tumor capsule in microvascular invasion with hepatocellular carcinoma: A spatial multi-omics study.PLoS medicine · 2026Article
- Extracellular and Membrane Protein: Structure, Biological Functions, Diseases, and an Emerging Modality for Drug Discovery.MedComm · 2026Review
- Heparan Sulfate Proteoglycans (HSPGs) and Their Degradation in Health and Disease.Biomolecules · 2025Review
- Curcumin protects extracellular matrix to maintain microenvironmental stability inhibiting colon cancer metastasis through HPSE/IL-6/STAT5 axis.Die Naturwissenschaften · 2025Article
- Necroptosis in obesity: a complex cell death event.Apoptosis : an international journal on programmed cell death · 2025Review
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- Heparanase interacting BCLAF1 to promote the development and drug resistance of ICC through the PERK/eIF2α pathway.Cancer gene therapy · 2024Article
- Pervasive loss of regulated necrotic cell death genes in elephants, hyraxes, and sea cows (bioRxiv : the preprint server for biology · 2024Article
- Exploration and validation of a novel signature of seven necroptosis-related genes to improve the clinical outcome of hepatocellular carcinoma.BMC cancer · 2023Article
- A necroptosis-related gene signature to predict prognosis and immune features in hepatocellular carcinoma.BMC cancer · 2023Article
- Classical epithelial-mesenchymal transition (EMT) and alternative cell death process-driven blebbishield metastatic-witch (BMW) pathways to cancer metastasis.Signal transduction and targeted therapy · 2022Review
- Multi-omics analysis reveals the panoramic picture of necroptosis-related regulators in pan-cancer.Aging · 2022Article
- A Novel Prognostic Predictor of Immune Microenvironment and Therapeutic Response in Kidney Renal Clear Cell Carcinoma based on Necroptosis-related Gene Signature.International journal of medical sciences · 2022Article
- Identification and Validation of Necroptosis-Related LncRNA Signature in Hepatocellular Carcinoma for Prognosis Estimation and Microenvironment Status.Frontiers in genetics · 2022Article
- A novel marker based on necroptosis-related long non-coding RNA for forecasting prognostic in patients with clear cell renal cell carcinoma.Frontiers in genetics · 2022Article
- A necroptosis-related lncRNA signature was identified to predict the prognosis and immune microenvironment of IDH-wild-type GBM.Frontiers in oncology · 2022Article
- Construction and Validation of a Necroptosis-Related Signature Associated With the Immune Microenvironment in Liver Hepatocellular Carcinoma.Frontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Heparanase (HPSE) is a kind of multifunctional extracellular hydrolase, and related to metastasis of hepatocellular carcinoma (HCC). Endothelial necroptosis promotes the metastasis of cancer cells. It is not clear whether HPSE could mediate necroptosis of microvascular endothelial cells (MVECs) to promote HCC metastasis. Here we found HPSE expression was up-regulated in HCC tissues and its over-expression was correlated with multiple tumor foci, microvascular invasion, and poor outcome of HCC patients. Non-contact co-culture experiments showed high-expressed HPSE in HCC cells mediated the necroptosis of human umbilical vein endothelial cells (HUVECs) and elevated the expression levels of syndecan-1 (SDC-1) and tumor necrosis factor-α (TNF-α) in vitro. As a result of necroptosis, trans-endothelial migration (TEM) of HCC cells was increased. Conversely, both HPSE and SDC-1 knockdowns reversed necroptosis and decreased TNF-α expression level, while HPSE over-expression increased SDC-1 and TNF-α expression and aggravated necroptosis. Animal experiments found that the nude mice, intraperitoneally injected with HPSE high expressing HCC cells, had obvious necroptosis of MVECs and high intrahepatic metastasis rate, which could be relieved by inhibitor of necroptosis. Morever, HPSE elevated the expression levels of p38 mitogen-activated protein kinase (p38 MAPK) rather than nuclear factor kappa B in vitro. Our data suggest that HPSE induces necroptosis of MVECs to promote the metastasis of HCC by activating HPSE/SDC-1/TNF-α axis and p38 MAPK pathway.
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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.