ArticleOncogene2016
Ceramide limits phosphatidylinositol-3-kinase C2β-controlled cell motility in ovarian cancer: potential of ceramide as a metastasis-suppressor lipid.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 52 citations in OpenAlex.
- Causal links between plasma lipidome and ovarian cancer risk: evidence from Mendelian randomization.Discover oncology · 2025Article
- Exploring the causal associations of the gut microbiota and plasma metabolites with ovarian cancer: an approach of mendelian randomization analysis combined with network pharmacology and molecular docking.Journal of ovarian research · 2025Article
- Article
- Inhibition of sphingolipid metabolism in osteosarcoma protects against CD151-mediated tumorigenicity.Cell & bioscience · 2022Article
- Widely Targeted Lipidomics and Transcriptomics Analysis Revealed Changes of Lipid Metabolism in Spleen Dendritic Cells in Shrimp Allergy.Foods (Basel, Switzerland) · 2022Article
- Article
- Ceramide synthase 2-CFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Circulating Lysophosphatidylcholines, Phosphatidylcholines, Ceramides, and Sphingomyelins and Ovarian Cancer Risk: A 23-Year Prospective Study.Journal of the National Cancer Institute · 2020Article
- CYonago acta medica · 2020Article
- Class II phosphatidylinositol 3-kinase α and β isoforms are required for vascular smooth muscle Rho activation, contraction and blood pressure regulation in mice.The journal of physiological sciences : JPS · 2020Article
- Review
- Sesquiterpene Alcohol Cedrol Chemosensitizes Human Cancer Cells and Suppresses Cell Proliferation by Destabilizing Plasma Membrane Lipid Rafts.Frontiers in cell and developmental biology · 2020Article
- The metabolic footprint during adipocyte commitment highlights ceramide modulation as an adequate approach for obesity treatment.EBioMedicine · 2020Article
- Metabolic Reprogramming and Epithelial-Mesenchymal Plasticity: Opportunities and Challenges for Cancer Therapy.Frontiers in oncology · 2020Review
- Downregulation of class II phosphoinositide 3-kinase PI3K-C2β delays cell division and potentiates the effect of docetaxel on cancer cell growth.Journal of experimental & clinical cancer research : CR · 2019Article
- Class II PI3Ks at the Intersection between Signal Transduction and Membrane Trafficking.Biomolecules · 2019Review
- The class II phosphoinositide 3-kinases PI3K-C2α and PI3K-C2β differentially regulate clathrin-dependent pinocytosis in human vascular endothelial cells.The journal of physiological sciences : JPS · 2019Article
- Ceramide-Graphene Oxide Nanoparticles Enhance Cytotoxicity and Decrease HCC Xenograft Development: A Novel Approach for Targeted Cancer Therapy.Frontiers in pharmacology · 2019Article
- Visualizing bioactive ceramides.Chemistry and physics of lipids · 2018Review
- Tyrosine kinase receptor TIE-1 mediates platinum resistance by promoting nucleotide excision repair in ovarian cancer.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Targeting cell motility, which is required for dissemination and metastasis, has therapeutic potential for ovarian cancer metastasis, and regulatory mechanisms of cell motility need to be uncovered for developing novel therapeutics. Invasive ovarian cancer cells spontaneously formed protrusions, such as lamellipodia, which are required for generating locomotive force in cell motility. Short interfering RNA screening identified class II phosphatidylinositol 3-kinase C2β (PI3KC2β) as the predominant isoform of PI3K involved in lamellipodia formation of ovarian cancer cells. The bioactive sphingolipid ceramide has emerged as an antitumorigenic lipid, and treatment with short-chain C6-ceramide decreased the number of ovarian cancer cells with PI3KC2β-driven lamellipodia. Pharmacological analysis demonstrated that long-chain ceramide regenerated from C6-ceramide through the salvage/recycling pathway, at least in part, mediated the action of C6-ceramide. Mechanistically, ceramide was revealed to interact with the PIK-catalytic domain of PI3KC2β and affect its compartmentalization, thereby suppressing PI3KC2β activation and its driven cell motility. Ceramide treatment also suppressed cell motility promoted by epithelial growth factor, which is a prometastatic factor. To examine the role of ceramide in ovarian cancer metastasis, ceramide liposomes were employed and confirmed to suppress cell motility in vitro. Ceramide liposomes had an inhibitory effect on peritoneal metastasis in a murine xenograft model of human ovarian cancer. Metastasis of PI3KC2β knocked-down cells was insensitive to treatment with ceramide liposomes, suggesting specific involvement of ceramide interaction with PI3KC2β in metastasis suppression. Our study identified ceramide as a bioactive lipid that limits PI3KC2β-governed cell motility, and ceramide is proposed to serve as a metastasis-suppressor lipid in ovarian cancer. These findings could be translated into developing ceramide-based therapy for metastatic diseases.
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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.