ArticleCellular signalling2013
The roles of sphingosine kinases 1 and 2 in regulating the Warburg effect in prostate cancer cells.
Article in Cellular signalling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 51 citations in OpenAlex.
- Lipids: Driving Forces in the Underlying Biology of Carcinogenesis.ACS pharmacology & translational science · 2025Review
- Targeting Sphingosine 1-Phosphate Metabolism as a Therapeutic Avenue for Prostate Cancer.Cancers · 2023Review
- 1-Deoxysphinganine initiates adaptive responses to serine and glycine starvation in cancer cells via proteolysis of sphingosine kinase.Journal of lipid research · 2022Article
- How cancer cells remodel lipid metabolism: strategies targeting transcription factors.Lipids in health and disease · 2021Review
- Sphingosine Kinase 1 Signaling in Breast Cancer: A Potential Target to Tackle Breast Cancer Stem Cells.Frontiers in molecular biosciences · 2021Review
- Sphingosine kinase 1 contributes to doxorubicin resistance and glycolysis in osteosarcoma.Molecular medicine reports · 2020Article
- Sphingosine Kinases are Involved in Macrophage NLRP3 Inflammasome Transcriptional Induction.International journal of molecular sciences · 2020Article
- Sphingosine-1-Phosphate in the Tumor Microenvironment: A Signaling Hub Regulating Cancer Hallmarks.Cells · 2020Review
- Lipids and cancer: Emerging roles in pathogenesis, diagnosis and therapeutic intervention.Advanced drug delivery reviews · 2020Review
- The Role of Herbal Bioactive Components in Mitochondria Function and Cancer Therapy.Evidence-based complementary and alternative medicine : eCAM · 2019Review
- Tissue proteomics outlines AGR2 AND LOX5 as markers for biochemical recurrence of prostate cancer.Oncotarget · 2018Article
- Synthesis of Novel FTY720 Analogs with Anticancer Activity through PP2A Activation.Molecules (Basel, Switzerland) · 2018Article
- Expansion of Sphingosine Kinase and Sphingosine-1-Phosphate Receptor Function in Normal and Cancer Cells: From Membrane Restructuring to Mediation of Estrogen Signaling and Stem Cell Programming.International journal of molecular sciences · 2018Review
- Novel Sphingolipid-Based Cancer Therapeutics in the Personalized Medicine Era.Advances in cancer research · 2018Review
- Interdiction of Sphingolipid Metabolism Revisited: Focus on Prostate Cancer.Advances in cancer research · 2018Review
- NMR metabolomics highlights sphingosine kinase-1 as a new molecular switch in the orchestration of aberrant metabolic phenotype in cancer cells.Molecular oncology · 2017Article
- Effect of sphingosine kinase modulators on interleukin-1β release, sphingosine 1-phosphate receptor 1 expression and experimental autoimmune encephalomyelitis.British journal of pharmacology · 2017Article
- Omentum and bone marrow: how adipocyte-rich organs create tumour microenvironments conducive for metastatic progression.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2016Review
- Bone marrow adipocytes promote the Warburg phenotype in metastatic prostate tumors via HIF-1α activation.Oncotarget · 2016Article
- Ceramide-tamoxifen regimen targets bioenergetic elements in acute myelogenous leukemia.Journal of lipid research · 2016Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Two isoforms of sphingosine kinase, SK1 and SK2, catalyze the formation of the bioactive lipid sphingosine 1-phosphate (S1P) in mammalian cells. We have previously shown that treatment of androgen-sensitive LNCaP prostate cancer cells with a non-selective SK isoform inhibitor, 2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole (SKi), induces the proteasomal degradation of SK1. This is concomitant with a significant increase in C22:0-ceramide and sphingosine levels and a reduction in S1P levels, resulting in the apoptosis of LNCaP cells. In contrast, we show here that a SK2-selective inhibitor, (R)-FTY720 methyl ether (ROME), increases sphingosine and decreases S1P levels but has no effect on ceramide levels and does not induce apoptosis in LNCaP cells. We also show that several glycolytic metabolites and (R)-S-lactoylglutathione are increased upon treatment of LNCaP cells with SKi, which induces the proteasomal degradation of c-Myc. These changes reflect an indirect antagonism of the Warburg effect. LNCaP cells also respond to SKi by diverting glucose 6-phosphate into the pentose phosphate pathway to provide NADPH, which serves as an antioxidant to counter an oxidative stress response. SKi also promotes the formation of a novel pro-apoptotic molecule called diadenosine 5',5'''-P(1),P(3)-triphosphate (Ap3A), which binds to the tumor suppressor fragile histidine triad protein (FHIT). In contrast, the SK2-selective inhibitor, ROME, induces a reduction in some glycolytic metabolites and does not affect oxidative stress. We conclude that SK1 functions to increase the stability of c-Myc and suppresses Ap3A formation, which might maintain the Warburg effect and cell survival, while SK2 exhibits a non-overlapping function.
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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.