ArticleOncotarget2015
HSulf-1 deficiency dictates a metabolic reprograming of glycolysis and TCA cycle in ovarian cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Cathepsin B-dependent glycolysis contributes to reduced renal uric acid excretion in hyperuricemia.Communications biology · 2025Article
- Phase Ib open-label, multicenter study of pixatimod, an activator of TLR9, in combination with nivolumab in subjects with microsatellite-stable metastatic colorectal cancer, metastatic pancreatic ductal adenocarcinoma and other solid tumors.Journal for immunotherapy of cancer · 2023Article
- Group III phospholipase A2 downregulation attenuated survival and metastasis in ovarian cancer and promotes chemo-sensitization.Journal of experimental & clinical cancer research : CR · 2021Article
- Ursolic Acid Inhibits Breast Cancer Metastasis by Suppressing Glycolytic MetabolismFrontiers in oncology · 2021Article
- Metabolomics analysis identifies lysine and taurine as candidate prognostic biomarkers for AML-M2 patients.International journal of hematology · 2020Article
- The Heparan Sulfate Mimetic PG545 Modulates T Cell Responses and Prevents Delayed-Type Hypersensitivity.Frontiers in immunology · 2020Article
- PFKFB3 inhibition reprograms malignant pleural mesothelioma to nutrient stress-induced macropinocytosis and ER stress as independent binary adaptive responses.Cell death & disease · 2019Article
- TIGAR promotes neural stem cell differentiation through acetyl-CoA-mediated histone acetylation.Cell death & disease · 2019Article
- Therapeutic targeting of PFKFB3 with a novel glycolytic inhibitor PFK158 promotes lipophagy and chemosensitivity in gynecologic cancers.International journal of cancer · 2019Article
- Oxidative Phosphorylation: A Target for Novel Therapeutic Strategies Against Ovarian Cancer.Cancers · 2018Review
- Sulfatase-1 knockdown promotes in vitro and in vivo aggressive behavior of murine hepatocarcinoma Hca-P cells through up-regulation of mesothelin.Journal of cell communication and signaling · 2018Article
- Immunomodulatory activities of pixatimod: emerging nonclinical and clinical data, and its potential utility in combination with PD-1 inhibitors.Journal for immunotherapy of cancer · 2018Article
- A Phase I study of the novel immunomodulatory agent PG545 (pixatimod) in subjects with advanced solid tumours.British journal of cancer · 2018Article
- Loss of HSulf-1: The Missing Link between Autophagy and Lipid Droplets in Ovarian Cancer.Scientific reports · 2017Article
- Metabolic Perturbation and Potential Markers in Patients with Esophageal Cancer.Gastroenterology research and practice · 2017Article
- Mechanisms of heparanase inhibitors in cancer therapy.Experimental hematology · 2016Review
- Methylglyoxal suppresses human colon cancer cell lines and tumor growth in a mouse model by impairing glycolytic metabolism of cancer cells associated with down-regulation of c-Myc expression.Cancer biology & therapy · 2016Article
- Disruption of the EZH2/miRNA/β-catenin signaling suppresses aerobic glycolysis in glioma.Oncotarget · 2016Article
- Review
- Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle.Open biology · 2016Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 4 countries.
Funding
Abstract
Warburg effect has emerged as a potential hallmark of many cancers. However, the molecular mechanisms that led to this metabolic state of aerobic glycolysis, particularly in ovarian cancer (OVCA) have not been completely elucidated. HSulf-1 predominantly functions by limiting the bioavailability of heparan binding growth factors and hence their downstream signaling. Here we report that HSulf-1, a known putative tumor suppressor, is a negative regulator of glycolysis. Silencing of HSulf-1 expression in OV202 cell line increased glucose uptake and lactate production by upregulating glycolytic genes such as Glut1, HKII, LDHA, as well as metabolites. Conversely, HSulf-1 overexpression in TOV21G cells resulted in the down regulation of glycolytic enzymes and reduced glycolytic phenotype, supporting the role of HSulf-1 loss in enhanced aerobic glycolysis. HSulf-1 deficiency mediated glycolytic enhancement also resulted in increased inhibitory phosphorylation of pyruvate dehydrogenase (PDH) thus blocking the entry of glucose flux into TCA cycle. Consistent with this, metabolomic and isotope tracer analysis showed reduced glucose flux into TCA cycle. Moreover, HSulf-1 loss is associated with lower oxygen consumption rate (OCR) and impaired mitochondrial function. Mechanistically, lack of HSulf-1 promotes c-Myc induction through HB-EGF-mediated p-ERK activation. Pharmacological inhibition of c-Myc reduced HB-EGF induced glycolytic enzymes implicating a major role of c-Myc in loss of HSulf-1 mediated altered glycolytic pathway in OVCA. Similarly, PG545 treatment, an agent that binds to heparan binding growth factors and sequesters growth factors away from their ligand also blocked HB-EGF signaling and reduced glucose uptake in vivo in HSulf-1 deficient cells.
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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.