ArticleMolecular cancer research : MCR2011
Ablation of sphingosine kinase-2 inhibits tumor cell proliferation and migration.
Article in Molecular cancer research : MCR, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 102 citations in OpenAlex.
- Phase II Trial of Opaganib Addition in Metastatic Castration-Resistant Prostate Cancer After Disease Progression on Abiraterone or Enzalutamide.Cancer medicine · 2026Trial
- Mechanisms and potential therapeutic targets of SphK1 and SphK2 in hepatocellular carcinoma.Frontiers in medicine · 2025Review
- Targeting sphingosine 1-phosphate and sphingosine kinases in pancreatic cancer: mechanisms and therapeutic potential.Cancer cell international · 2024Review
- A chemical screen for modulators of mRNA translation identifies a distinct mechanism of toxicity for sphingosine kinase inhibitors.PLoS biology · 2021Article
- Inhibition of sphingosine kinase 2 down-regulates ERK/c-Myc pathway and reduces cell proliferation in human epithelial ovarian cancer.Annals of translational medicine · 2021Article
- SphK2/S1P Promotes Metastasis of Triple-Negative Breast Cancer Through the PAK1/LIMK1/Cofilin1 Signaling Pathway.Frontiers in molecular biosciences · 2021Article
- Profile of Basal Cell Carcinoma Mutations and Copy Number Alterations - Focus on Gene-Associated Noncoding Variants.Frontiers in oncology · 2021Article
- Lipid Phosphate Phosphatases and Cancer.Biomolecules · 2020Review
- Follicle-stimulating hormone promotes the proliferation of epithelial ovarian cancer cells by activating sphingosine kinase.Scientific reports · 2020Article
- Modulation of DNA Damage Response by Sphingolipid Signaling: An Interplay that Shapes Cell Fate.International journal of molecular sciences · 2020Review
- Article
- Metabolic Plasticity in Chemotherapy Resistance.Frontiers in oncology · 2020Review
- S1P/S1P Receptor Signaling in Neuromuscolar Disorders.International journal of molecular sciences · 2019Review
- Sphingolipid metabolism and drug resistance in ovarian cancer.Cancer drug resistance (Alhambra, Calif.) · 2018Article
- Targeting Sphingosine Kinase Isoforms Effectively Reduces Growth and Survival of Neoplastic Mast Cells With D816V-KIT.Frontiers in immunology · 2018Article
- SphK2 over-expression promotes osteosarcoma cell growth.Oncotarget · 2017Article
- A Phase I Study of ABC294640, a First-in-Class Sphingosine Kinase-2 Inhibitor, in Patients with Advanced Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Sphingosine kinase 2 activates autophagy and protects neurons against ischemic injury through interaction with Bcl-2 via its putative BH3 domain.Cell death & disease · 2017Article
- Mammalian sphingosine kinase (SphK) isoenzymes and isoform expression: challenges for SphK as an oncotarget.Oncotarget · 2017Review
- RNAi screen reveals a role of SPHK2 in dengue virus-mediated apoptosis in hepatic cell lines.PloS one · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Sphingosine kinases (SK) regulate the balance between proapoptotic ceramides and mitogenic sphingosine-1-phosphate (S1P); however, the functions of the two isoenzymes (SK1 and SK2) in tumor cells are not well defined. Therefore, RNA interference was used to assess the individual roles of SK1 and SK2 in tumor cell sphingolipid metabolism, proliferation, and migration/invasion. Treatment of A498, Caki-1, or MDA-MB-231 cells with siRNAs specific for SK1 or SK2 effectively suppressed the expression of the target mRNA and protein. Ablation of SK1 did not affect mRNA or protein levels of SK2 and reduced intracellular levels of S1P while elevating ceramide levels. In contrast, ablation of SK2 elevated mRNA, protein, and activity levels of SK1 and increased cellular S1P levels. Interestingly, cell proliferation and migration/invasion were suppressed more by SK2-selective ablation than by SK1-selective ablation, showing that the increased S1P does not rescue these phenotypes. Similarly, exogenous S1P did not rescue the cells from the antiproliferative or antimigratory effects of the siRNAs. Consistent with these results, differential effects of SK1- and SK2-selective siRNAs on signaling proteins, including p53, p21, ERK1, ERK2, FAK, and VCAM1, indicate that SK1 and SK2 have only partially overlapping functions in tumor cells. Overall, these data indicate that loss of SK2 has stronger anticancer effects than does suppression of SK1. Consequently, selective inhibitors of SK2 may provide optimal targeting of this pathway in cancer chemotherapy.
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Registered trials
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