ArticleThe Journal of biological chemistry2012
Heparanase enhances the insulin receptor signaling pathway to activate extracellular signal-regulated kinase in multiple myeloma.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Molecular Insights in Uterine Leiomyosarcoma: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Mast cell heparanase promotes breast cancer stem-like features via MUC1/estrogen receptor axis.Cell death & disease · 2024Article
- Heparanase-A single protein with multiple enzymatic and nonenzymatic functions.Proteoglycan research · 2023Review
- Heparanase contributes to pancreatic carcinoma progression through insulin-dependent glucose uptake.Frontiers in cell and developmental biology · 2023Article
- Review
- Heparanase overexpression impedes perivascular clearance of amyloid-β from murine brain: relevance to Alzheimer's disease.Acta neuropathologica communications · 2021Article
- Endothelial Glycocalyx as a Regulator of Fibrotic Processes.International journal of molecular sciences · 2021Review
- Dichotomic role of heparanase in a murine model of metabolic syndrome.Cellular and molecular life sciences : CMLS · 2021Article
- Heparanase, cell signaling, and viral infections.Cellular and molecular life sciences : CMLS · 2020Review
- Heparanase: A Dynamic Promoter of Myeloma Progression.Advances in experimental medicine and biology · 2020Review
- Regulation of Heparanase in Diabetes-Associated Pancreatic Carcinoma.Frontiers in oncology · 2019Article
- Identification of key genes and pathways in uterine leiomyosarcoma through bioinformatics analysis.Oncology letters · 2018Article
- Chemotherapy induces secretion of exosomes loaded with heparanase that degrades extracellular matrix and impacts tumor and host cell behavior.Matrix biology : journal of the International Society for Matrix Biology · 2018Article
- Heparan Sulfate Glycosaminoglycans in Glioblastoma Promote Tumor Invasion.Molecular cancer research : MCR · 2017Article
- Heparanase augments insulin receptor signaling in breast carcinoma.Oncotarget · 2017Article
- High glucose facilitated endothelial heparanase transfer to the cardiomyocyte modifies its cell death signature.Cardiovascular research · 2016Article
- Mechanisms of heparanase inhibitors in cancer therapy.Experimental hematology · 2016Review
- Insights into the molecular roles of heparan sulfate proteoglycans (HSPGs-syndecans) in autocrine and paracrine growth factor signaling in the pathogenesis of Hodgkin's lymphoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Heparanase promotes myeloma progression by inducing mesenchymal features and motility of myeloma cells.Oncotarget · 2016Article
- Human telomerase reverse transcriptase (hTERT) promotes gastric cancer invasion through cooperating with c-Myc to upregulate heparanase expression.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
ERK signaling regulates proliferation, survival, drug resistance, and angiogenesis in cancer. Although the mechanisms regulating ERK activation are not fully understood, we previously demonstrated that ERK phosphorylation is elevated by heparanase, an enzyme associated with aggressive behavior of many cancers. In the present study, myeloma cell lines expressing either high or low levels of heparanase were utilized to determine how heparanase stimulates ERK signaling. We discovered that the insulin receptor was abundant on cells expressing either high or low levels of heparanase, but the receptor was highly phosphorylated in heparanase-high cells compared with heparanase-low cells. In addition, protein kinase C activity was elevated in heparanase-high cells, and this enhanced expression of insulin receptor substrate-1 (IRS-1), the principle intracellular substrate for phosphorylation by the insulin receptor. Blocking insulin receptor function with antibody or a small molecule inhibitor or knockdown of IRS-1 expression using shRNA diminished heparanase-mediated ERK activation in the tumor cells. In addition, up-regulation of the insulin signaling pathway by heparanase and the resulting ERK activation were dependent on heparanase retaining its enzyme activity. These results reveal a novel mechanism whereby heparanase enhances activation of the insulin receptor signaling pathway leading to ERK activation and modulation of myeloma behavior.
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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.