ArticleNeoplasia (New York, N.Y.)2015
Lysophosphatidic Acid Up-Regulates Hexokinase II and Glycolysis to Promote Proliferation of Ovarian Cancer Cells.
Article in Neoplasia (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 54 citations in OpenAlex.
- Glycolytic reprogramming in ovarian cancer: mechanisms, immune crosstalk, and therapeutic implications.Frontiers in immunology · 2026Review
- Decoding lysophosphatidic acid signaling in physiology and disease: mapping the multimodal and multinodal signaling networks.Signal transduction and targeted therapy · 2025Review
- SRC enhanced cisplatin resistance in bladder cancer by reprogramming glycolysis and pentose phosphate pathway.Communications biology · 2025Article
- Spatial profiling of the metabolism-immune axis in ovarian cancer.Frontiers in pharmacology · 2025Review
- Hexokinase 2 promotes tumor development and progression.American journal of cancer research · 2025Review
- miR-203-3p promotes senescence of mouse bone marrow mesenchymal stem cells via downregulation of Pbk.Aging cell · 2024Article
- LPAR2-mediated action promotes human renal cell carcinoma via MAPK/NF-κB signaling to regulate cytokine network.Journal of cancer research and clinical oncology · 2023Article
- Molecular mechanisms of microRNA-216a during tumor progression.Cancer cell international · 2023Review
- Research progress on the mechanism of glycolysis in ovarian cancer.Frontiers in immunology · 2023Review
- Metabolic reprogramming of three major nutrients in platinum-resistant ovarian cancer.Frontiers in oncology · 2023Review
- Targeting lysophosphatidic acid receptor with Ki16425 impedes T cell lymphoma progression through apoptosis induction, glycolysis inhibition, and activation of antitumor immune response.Apoptosis : an international journal on programmed cell death · 2022Article
- PI3K-AKT Pathway Modulation by Thymoquinone Limits Tumor Growth and Glycolytic Metabolism in Colorectal Cancer.International journal of molecular sciences · 2022Article
- Hexokinases 2 promoted cell motility and distant metastasis by elevating fibronectin through Akt1/p-Akt1 in cervical cancer cells.Cancer cell international · 2021Article
- Lysophosphatidic Acid Induces Aerobic Glycolysis, Lipogenesis, and Increased Amino Acid Uptake in BV-2 Microglia.International journal of molecular sciences · 2021Article
- Activation of Macrophages by Lysophosphatidic Acid through the Lysophosphatidic Acid Receptor 1 as a Novel Mechanism in Multiple Sclerosis Pathogenesis.Molecular neurobiology · 2021Article
- Role of lysophosphatidic acid and its receptors in health and disease: novel therapeutic strategies.Signal transduction and targeted therapy · 2021Review
- Metabolic reprogramming in epithelial ovarian cancer.American journal of translational research · 2021Review
- A novel lncRNA PTTG3P/miR-132/212-3p/FoxM1 feedback loop facilitates tumorigenesis and metastasis of pancreatic cancer.Cell death discovery · 2020Article
- Lipid Regulatory Proteins as Potential Therapeutic Targets for Ovarian Cancer in Obese Women.Cancers · 2020Review
- MicroRNA-615 functions as a tumor suppressor in osteosarcoma through the suppression of HK2.Oncology letters · 2020Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Lysophosphatidic acid (LPA), a blood-borne lipid mediator, is present in elevated concentrations in ascites of ovarian cancer patients and other malignant effusions. LPA is a potent mitogen in cancer cells. The mechanism linking LPA signal to cancer cell proliferation is not well understood. Little is known about whether LPA affects glucose metabolism to accommodate rapid proliferation of cancer cells. Here we describe that in ovarian cancer cells, LPA enhances glycolytic rate and lactate efflux. A real time PCR-based miniarray showed that hexokinase II (HK2) was the most dramatically induced glycolytic gene to promote glycolysis in LPA-treated cells. Analysis of the human HK2 gene promoter identified the sterol regulatory element-binding protein as the primary mediator of LPA-induced HK2 transcription. The effects of LPA on HK2 and glycolysis rely on LPA2, an LPA receptor subtype overexpressed in ovarian cancer and many other malignancies. We further examined the general role of growth factor-induced glycolysis in cell proliferation. Like LPA, epidermal growth factor (EGF) elicited robust glycolytic and proliferative responses in ovarian cancer cells. Insulin-like growth factor 1 (IGF-1) and insulin, however, potently stimulated cell proliferation but only modestly induced glycolysis. Consistent with their differential effects on glycolysis, LPA and EGF-dependent cell proliferation was highly sensitive to glycolytic inhibition while the growth-promoting effect of IGF-1 or insulin was more resistant. These results indicate that LPA- and EGF-induced cell proliferation selectively involves up-regulation of HK2 and glycolytic metabolism. The work is the first to implicate LPA signaling in promotion of glucose metabolism in cancer cells.
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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.