ArticleOncotarget2016
Sphingosine kinase 1 is required for TGF-β mediated fibroblastto- myofibroblast differentiation in ovarian cancer.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Integration of metabolites from meta-analysis with transcriptome reveals enhanced SPHK1 in PDAC with a background of pancreatitis.BMC cancer · 2022Pooled it
- Suppression of Post-Ischemic Cardiac Remodelling and Inflammatory Response by a Novel Sphingolipid Modifier, CIN038.International journal of molecular sciences · 2026Article
- Targeting SPHK1 by 8-HETrE attenuates MASH-Driven fibrosis via restoration of hepatic stellate cell mitochondrial dynamics.Cell biology and toxicology · 2026Article
- Article
- Receptor Co‑targeting Strategies for Personalized Ovarian Cancer Therapy.International journal of nanomedicine · 2026Review
- Role of metabolic reprogramming of cancer‑associated fibroblasts in tumor development and progression (Review).International journal of oncology · 2025Review
- Sphingosine 1-phosphate derived from tumor-educated hepatic stellate cells combining with S1PR4 promotes tumor associated macrophages differentiation through FAO modulation.Scientific reports · 2025Article
- Identification of Sphingosine Kinase 1 as a Novel Protein Regulated by High Molecular Weight Hyaluronan in Ovarian Cancer.Journal of cellular and molecular medicine · 2025Article
- SPHK1-mediated M2 macrophage polarization drives TGF-β1-dependent thrombus fibrosis.Frontiers in immunology · 2025Article
- Pan-cancer analyses reveal cancer-type-specific autophagy signatures with potential implications for prognosis and therapy response.Journal of Cancer · 2025Article
- Gα12 and Gα13 proteins are required for transforming growth factor-β-induced myofibroblast differentiation.The Biochemical journal · 2024Article
- Synergistic effect of the sphingosine kinase inhibitor safingol in combination with 2'-nitroflavone in breast cancer.Journal of molecular medicine (Berlin, Germany) · 2024Article
- Targeting sphingosine 1-phosphate and sphingosine kinases in pancreatic cancer: mechanisms and therapeutic potential.Cancer cell international · 2024Review
- Critical role of Gα12 and Gα13 proteins in TGF-β-induced myofibroblast differentiation.bioRxiv : the preprint server for biology · 2024Article
- Tertiary lymphoid structures and B cells determine clinically relevant T cell phenotypes in ovarian cancer.Nature communications · 2024Article
- INHBA(+) cancer-associated fibroblasts generate an immunosuppressive tumor microenvironment in ovarian cancer.NPJ precision oncology · 2024Article
- Dietary fat and lipid metabolism in the tumor microenvironment.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Inhibitory Effect of Resveratrol on LPS-induced Glomerular Mesangial Cells Proliferation and TGF-β1 Expression via Sphingosine Kinase 1 Pathway.Chinese journal of integrative medicine · 2023Article
- Cancer-associated fibroblasts in gynecological malignancies: are they really allies of the enemy?Frontiers in oncology · 2023Review
- Expression of sphingosine-1-phosphate receptor 2 is correlated with migration and invasion of human colon cancer cells: A preliminary clinical study.Oncology letters · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Sphingosine kinase 1 (SPHK1), the enzyme that produces sphingosine 1 phosphate (S1P), is known to be highly expressed in many cancers. However, the role of SPHK1 in cells of the tumor stroma remains unclear. Here, we show that SPHK1 is highly expressed in the tumor stroma of high-grade serous ovarian cancer (HGSC), and is required for the differentiation and tumor promoting function of cancer-associated fibroblasts (CAFs). Knockout or pharmacological inhibition of SPHK1 in ovarian fibroblasts attenuated TGF-β-induced expression of CAF markers, and reduced their ability to promote ovarian cancer cell migration and invasion in a coculture system. Mechanistically, we determined that SPHK1 mediates TGF-β signaling via the transactivation of S1P receptors (S1PR2 and S1PR3), leading to p38 MAPK phosphorylation. The importance of stromal SPHK1 in tumorigenesis was confirmed in vivo, by demonstrating a significant reduction of tumor growth and metastasis in SPHK1 knockout mice. Collectively, these findings demonstrate the potential of SPHK1 inhibition as a novel stroma-targeted therapy in HGSC.
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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.