ArticleOncotarget2014
Assessment of the effect of sphingosine kinase inhibitors on apoptosis,unfolded protein response and autophagy of T-cell acute lymphoblastic leukemia cells; indications for novel therapeutics.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Is Sphingosine Kinase 1 Associated with Hematological Malignancy? A Systematic Review and Meta-Analysis.Asian Pacific journal of cancer prevention : APJCP · 2024Pooled it
- Synergistic Molecular Strategies for Targeting the Unfolded Protein Response in Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- The role of sphingosine-1-phosphate in autophagy and related disorders.Cell death discovery · 2023Review
- Orchestral role of lipid metabolic reprogramming in T-cell malignancy.Frontiers in oncology · 2023Review
- Metabolism in Hematopoiesis and Its Malignancy.Advances in experimental medicine and biology · 2023Article
- ER Stress and Unfolded Protein Response in Leukemia: Friend, Foe, or Both?Biomolecules · 2021Review
- Review
- Metabolic dependencies and vulnerabilities in leukemia.Genes & development · 2019Review
- Native and Polyubiquitinated Forms of Dihydroceramide Desaturase Are Differentially Linked to Human Embryonic Kidney Cell Survival.Molecular and cellular biology · 2018Article
- Novel Sphingolipid-Based Cancer Therapeutics in the Personalized Medicine Era.Advances in cancer research · 2018Review
- Sphingosine kinase 2 supports the development of BCR/ABL-independent acute lymphoblastic leukemia in mice.Biomarker research · 2018Article
- Targeting sphingolipid metabolism as an approach for combination therapies in haematological malignancies.Cell death discovery · 2018Article
- Sphingosine kinase 2 and multiple myeloma.Oncotarget · 2017Article
- SGPL1 (sphingosine phosphate lyase 1) modulates neuronal autophagy via phosphatidylethanolamine production.Autophagy · 2017Article
- Therapeutic potential of targeting sphingosine kinases and sphingosine 1-phosphate in hematological malignancies.Leukemia · 2016Review
- Intracellular Signaling Pathways Involved in Childhood Acute Lymphoblastic Leukemia; Molecular Targets.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2016Review
- Exploring the role of sphingolipid machinery during the epithelial to mesenchymal transition program using an integrative approach.Oncotarget · 2016Article
- Targeting autophagy to sensitive glioma to temozolomide treatment.Journal of experimental & clinical cancer research : CR · 2016Review
- Sphingosine-1-Phosphate Induces Dose-Dependent Chemotaxis or Fugetaxis of T-ALL Blasts through S1P1 Activation.PloS one · 2016Article
- Proteolytic systems and AMP-activated protein kinase are critical targets of acute myeloid leukemia therapeutic approaches.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
15 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sphingosine 1-phosphate (S1P) is a bioactive lipid that is formed by the phosphorylation of sphingosine and catalysed by sphingosine kinase 1 (SK1) or sphingosine kinase 2 (SK2). Sphingosine kinases play a fundamental role in many signaling pathways associated with cancer, suggesting that proteins belonging to this signaling network represent potential therapeutic targets. Over the last years, many improvements have been made in the treatment of T-cell acute lymphoblastic leukemia (T-ALL); however, novel and less toxic therapies are still needed, especially for relapsing and chemo-resistant patients. Here, we analyzed the therapeutic potential of SKi and ROMe, a sphingosine kinase 1 and 2 inhibitor and SK2-selective inhibitor, respectively. While SKi induced apoptosis, ROMe initiated an autophagic cell death in our in vitro cell models. SKi treatment induced an increase in SK1 protein levels in Molt-4 cells, whereas it activated the endoplasmic reticulum (ER) stress/unfolded protein response (UPR) pathway in Jurkat and CEM-R cells as protective mechanisms in a sub-population of T-ALL cells. Interestingly, we observed a synergistic effect of SKi with the classical chemotherapeutic drug vincristine. In addition, we reported that SKi affected signaling cascades implicated in survival, proliferation and stress response of cells. These findings indicate that SK1 or SK2 represent potential targets for treating T-ALL.
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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.