Abstract
Sphingolipid metabolites are critical to the regulation of a number of fundamental biological processes including cancer. Whereas ceramide and sphingosine mediate and trigger apoptosis or cell growth arrest, sphingosine 1- phosphate promotes proliferation, cell survival and angiogenesis. The delicate equilibrium between the intracellular levels of each of these sphingolipids is controlled by the enzymes that either produce or degrade these metabolites. Sphingosine kinase-1 is a crucial regulator of this two-pan balance, because it produces the pro-survival and pro-angiogenic sphingosine 1-phosphate and decreases the amount of both ceramide and sphingosine, the pro-apoptotic sphingolipids. Moreover, its gene is oncogenic, its mRNA is overproduced in several solid tumors, its overexpression protects cells from apoptosis, and its activity is down-regulated by anti-cancer treatments. Therefore, the sphingosine kinase-1/sphingosine 1-phosphate signaling pathway appears to be a target of interest for therapeutic manipulation.
Keywords: Antagonists, &, inhibitors, ceramide, sphingolipids, sphingosine, sphingosine kinase-1, sphingosine 1-phosphate, therapeutic antibody
Current Molecular Pharmacology
Title: Activation of Sphingosine Kinase-1 in Cancer: Implications for Therapeutic Targeting
Volume: 3
Author(s): Olivier Cuvillier, Isabelle Ader, Pierre Bouquerel, Leyre Brizuela, Bernard Malavaud, Catherine Mazerolles and Pascal Rischmann
Affiliation:
Keywords: Antagonists, &, inhibitors, ceramide, sphingolipids, sphingosine, sphingosine kinase-1, sphingosine 1-phosphate, therapeutic antibody
Abstract: Sphingolipid metabolites are critical to the regulation of a number of fundamental biological processes including cancer. Whereas ceramide and sphingosine mediate and trigger apoptosis or cell growth arrest, sphingosine 1- phosphate promotes proliferation, cell survival and angiogenesis. The delicate equilibrium between the intracellular levels of each of these sphingolipids is controlled by the enzymes that either produce or degrade these metabolites. Sphingosine kinase-1 is a crucial regulator of this two-pan balance, because it produces the pro-survival and pro-angiogenic sphingosine 1-phosphate and decreases the amount of both ceramide and sphingosine, the pro-apoptotic sphingolipids. Moreover, its gene is oncogenic, its mRNA is overproduced in several solid tumors, its overexpression protects cells from apoptosis, and its activity is down-regulated by anti-cancer treatments. Therefore, the sphingosine kinase-1/sphingosine 1-phosphate signaling pathway appears to be a target of interest for therapeutic manipulation.
Export Options
About this article
Cite this article as:
Cuvillier Olivier, Ader Isabelle, Bouquerel Pierre, Brizuela Leyre, Malavaud Bernard, Mazerolles Catherine and Rischmann Pascal, Activation of Sphingosine Kinase-1 in Cancer: Implications for Therapeutic Targeting, Current Molecular Pharmacology 2010; 3 (2) . https://dx.doi.org/10.2174/1874467211003020053
DOI https://dx.doi.org/10.2174/1874467211003020053 |
Print ISSN 1874-4672 |
Publisher Name Bentham Science Publisher |
Online ISSN 1874-4702 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Ligand-Based Pharmacophore Modeling, Atom-Based 3D-QSAR and Molecular Docking Studies on Substituted Thiazoles and Thiophenes as Polo-Like Kinase 1 (Plk1) Inhibitors
Combinatorial Chemistry & High Throughput Screening Emerging Immunotargets in Bladder Cancer
Current Drug Targets Recent Advances of Metallocenes for Medicinal Chemistry
Mini-Reviews in Medicinal Chemistry Anti-tumor Therapeutic Molecules that Target the Programmed Cell Death Machinery
Mini-Reviews in Medicinal Chemistry Remodelling of the Ca2+ Toolkit in Tumor Endothelium as a Crucial Responsible for the Resistance to Anticancer Therapies
Current Signal Transduction Therapy HuR as Therapeutic Target in Cancer: What the Future Holds
Current Medicinal Chemistry Chemistry and Pharmacology of Neglected Helminthic Diseases
Current Medicinal Chemistry Activation of PI3K/Akt/mTOR Pathway and Dual Inhibitors of PI3K and mTOR in Endometrial Cancer
Current Medicinal Chemistry Biocatalysis in the Pharmaceutical Industry. A Greener Future
Current Green Chemistry LncRNA as a Therapeutic Target for Angiogenesis
Current Topics in Medicinal Chemistry New Generation of Oncolytic Herpes Virus
Current Cancer Therapy Reviews Cholecystokinin Antagonists A New Way to Improve the Analgesia from Old Analgesics?
Current Pharmaceutical Design 2D QSAR Studies on a Series of Quinazoline Derivatives as Tyrosine Kinase (EGFR) Inhibitor: An Approach to Design Anticancer Agents
Letters in Drug Design & Discovery Recent Patents in Glycan-Based Cancer Biomarkers and Discovery Technologies
Recent Patents on Biomarkers (Iso)Flav(an)ones, Chalcones, Catechins, and Theaflavins as Anticarcinogens: Mechanisms, Anti-Multidrug Resistance and QSAR Studies
Current Medicinal Chemistry New Potential Serum Biomarkers in Multiple Sclerosis Identified by Proteomic Strategies
Current Medicinal Chemistry Current Understanding of the Potential of Proteomics and Metabolomics Approaches in Cancer Chemoresistance: A Focus on Multiple Myeloma
Current Topics in Medicinal Chemistry TRAIL Gene Therapy: From Preclinical Development to Clinical Application
Current Gene Therapy Regulatory T Cells and Cancer Therapy: An Old Story with a New Hope
Current Cancer Therapy Reviews Role of Inflammatory Mediators in Angiogenesis
Current Drug Targets - Inflammation & Allergy