ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015
A novel role of sphingosine kinase-1 in the invasion and angiogenesis of VHL mutant clear cell renal cell carcinoma.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 53 citations in OpenAlex.
- Machine learning models to identify lead compound and substitution optimization to have derived energetics and conformational stability through docking and MD simulations for sphingosine kinase 1.Molecular diversity · 2025Article
- A Novel KIF4A-related Model for Predicting Immunotherapy Response and Prognosis in Kidney Renal Clear Cell Carcinoma.Combinatorial chemistry & high throughput screening · 2025Article
- The Sphingosine 1-Phosphate Axis: an Emerging Therapeutic Opportunity for Endometriosis.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- Upregulation of sphingosine kinase 1 in response to doxorubicin generates an angiogenic response via stabilization of Snail.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Lipids as Targets for Renal Cell Carcinoma Therapy.International journal of molecular sciences · 2023Review
- Deregulated expression of the 14q32 miRNA cluster in clear cell renal cancer cells.Frontiers in oncology · 2023Article
- Mebendazole Impedes the Proliferation and Migration of Pancreatic Cancer Cells through SK1 Inhibition Dependent Pathway.Molecules (Basel, Switzerland) · 2022Article
- Establishment of a prognostic ferroptosis- and immune-related long noncoding RNAs profile in kidney renal clear cell carcinoma.Frontiers in genetics · 2022Article
- Article
- Extracellular Sphingosine-1-Phosphate Downstream of EGFR Increases Human Glioblastoma Cell Survival.International journal of molecular sciences · 2021Article
- The Role of Ceramide Metabolism and Signaling in the Regulation of Mitophagy and Cancer Therapy.Cancers · 2021Review
- Bioactive sphingolipids: Advancements and contributions from the laboratory of Dr. Lina M. Obeid.Cellular signalling · 2021Review
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- Autophagy-related geneAging · 2020Article
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- Bioactive lysolipids in cancer and angiogenesis.Pharmacology & therapeutics · 2019Review
- Overexpression of SNHG12 regulates the viability and invasion of renal cell carcinoma cells through modulation of HIF1α.Cancer cell international · 2019Article
- Functional Long Noncoding RNAs (lncRNAs) in Clear Cell Kidney Carcinoma Revealed by Reconstruction and Comprehensive Analysis of the lncRNA-miRNA-mRNA Regulatory Network.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Molecular mechanisms of regulation of sphingosine kinase 1.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2018Review
- Conjugated Bile Acids Promote Invasive Growth of Esophageal Adenocarcinoma Cells and Cancer Stem Cell Expansion via Sphingosine 1-Phosphate Receptor 2-Mediated Yes-Associated Protein Activation.The American journal of pathology · 2018Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Sphingosine kinase 1 (SK1), the enzyme responsible for sphingosine 1-phosphate (S1P) production, is overexpressed in many human solid tumors. However, its role in clear cell renal cell carcinoma (ccRCC) has not been described previously. ccRCC cases are usually associated with mutations in von Hippel-Lindau (VHL) and subsequent normoxic stabilization of hypoxia-inducible factor (HIF). We previously showed that HIF-2α up-regulates SK1 expression during hypoxia in glioma cells. Therefore, we hypothesized that the stabilized HIF in ccRCC cells will be associated with increased SK1 expression. Here, we demonstrate that SK1 is overexpressed in 786-0 renal carcinoma cells lacking functional VHL, with concomitant high S1P levels that appear to be HIF-2α mediated. Moreover, examining the TCGA RNA seq database shows that SK1 expression was ∼2.7-fold higher in solid tumor tissue from ccRCC patients, and this was associated with less survival. Knockdown of SK1 in 786-0 ccRCC cells had no effect on cell proliferation. On the other hand, this knockdown resulted in an ∼3.5-fold decrease in invasion, less phosphorylation of focal adhesion kinase (FAK), and an ∼2-fold decrease in angiogenesis. Moreover, S1P treatment of SK1 knockdown cells resulted in phosphorylation of FAK and invasion, and this was mediated by S1P receptor 2. These results suggest that higher SK1 and S1P levels in VHL-defective ccRCC could induce invasion in an autocrine manner and angiogenesis in a paracrine manner. Accordingly, targeting SK1 could reduce both the invasion and angiogenesis of ccRCC and therefore improve the survival rate of patients.
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