ArticleOncology reports2012
Dual inhibition of sphingosine kinase isoforms ablates TNF-induced drug resistance.
Article in Oncology reports, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Sphingolipid-Neuroinflammation Axis in Parkinson's Disease: Focus on S1P/SPHK1-NF‑κB Signaling.Journal of inflammation research · 2026Review
- Sphingosine-1-Phosphate Metabolic Pathway in Cancer: Implications for Therapeutic Targets.International journal of molecular sciences · 2025Review
- Role of Sphingosine-1-Phosphate Signaling Pathway in Pancreatic Diseases.International journal of molecular sciences · 2024Review
- Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-α immunotherapy.Cell communication and signaling : CCS · 2024Review
- The key role of sphingolipid metabolism in cancer: New therapeutic targets, diagnostic and prognostic values, and anti-tumor immunotherapy resistance.Frontiers in oncology · 2022Review
- Targeting Sphingolipids for Cancer Therapy.Frontiers in oncology · 2021Review
- Consequences of EMT-Driven Changes in the Immune Microenvironment of Breast Cancer and Therapeutic Response of Cancer Cells.Journal of clinical medicine · 2019Review
- Inhibition of breast tumor growth in mice after treatment with ceramide analog 315.Anti-cancer drugs · 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
- Elevated expression of long intergenic non-coding RNA HOTAIR in a basal-like variant of MCF-7 breast cancer cells.Molecular carcinogenesis · 2015Article
- Evolving concepts in cancer therapy through targeting sphingolipid metabolism.Biochimica et biophysica acta · 2014Review
- Re-configuration of sphingolipid metabolism by oncogenic transformation.Biomolecules · 2014Review
- Retinal upregulation of inflammatory and proangiogenic markers in a model of neonatal diabetic rats fed on a high-fat-diet.BMC ophthalmology · 2013Article
- Inhibition of p38 mitogen-activated protein kinase alters microRNA expression and reverses epithelial-to-mesenchymal transition.International journal of oncology · 2013Article
- Novel chemotherapeutic drugs in sphingolipid cancer research.Handbook of experimental pharmacology · 2013Review
- Antiestrogenic activity of flavonoid phytochemicals mediated via the c-Jun N-terminal protein kinase pathway. Cell-type specific regulation of estrogen receptor alpha.The Journal of steroid biochemistry and molecular biology · 2012Article
- Sphingosine kinase isoforms as a therapeutic target in endocrine therapy resistant luminal and basal-A breast cancer.Experimental biology and medicine (Maywood, N.J.) · 2012Article
- Altered death receptor signaling promotes epithelial-to-mesenchymal transition and acquired chemoresistance.Scientific reports · 2012Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Recent research has demonstrated that aberrant sphingolipid signaling is an important mechanism of chemoresistance in solid tumors. Sphingosine kinase (Sphk), the primary enzyme metabolizing the sphingolipid ceramide into sphingosine-1-phosphate (S1P), is a primary mediator of breast cancer promotion, survival and chemoresistance. However, to date the mechanism of Sphk-mediated drug resistance is poorly understood. Using the dual sphingosine kinase isozyme inhibitor, SKI-II (4-[4-(4-chloro-phenyl)-thiazol-2-ylamino]-phenol), we explored the effects of sphingosine kinase inhibition on multi-drug-resistant breast cancer cells. We demonstrate that SKI-II alters endogenous sphingolipid signaling and decreases cancer proliferation, survival and viability. Furthermore, pharmacological inhibition of Sphk1/2 induced intrinsic apoptosis in these cells through modulation of the NF-κB pathway. SKI-II decreases NF-κB transcriptional activity through altered phosphorylation of the p65 subunit. Taken together, these results suggest that Sphk may be a promising therapeutic target in chemoresistant cancers.
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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.