Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond
Reads0
Chats0
TLDR
The ways in which S1P might be therapeutically targeted are discussed — for example, via the development of chemical inhibitors that target the generation, transport and degradation of S 1P and via thedevelopment of specific S1p receptor agonists.Abstract:
The bioactive lipid sphingosine-1-phosphate (S1P) is involved in multiple cellular signalling systems and has a pivotal role in the control of immune cell trafficking. As such, S1P has been implicated in disorders such as cancer and inflammatory diseases. This Review discusses the ways in which S1P might be therapeutically targeted — for example, via the development of chemical inhibitors that target the generation, transport and degradation of S1P and via the development of specific S1P receptor agonists. We also highlight recent conflicting results observed in preclinical studies targeting S1P and discuss ongoing clinical trials in this field.read more
Citations
More filters
Journal ArticleDOI
Metastatic triple-negative breast cancer is dependent on SphKs/S1P signaling for growth and survival
TL;DR: This study highlights the importance of SphKs/S1P signaling in metastatic triple-negative breast cancers and targeted therapies.
Journal ArticleDOI
Differential S1P Receptor Profiles on M1- and M2-Polarized Macrophages Affect Macrophage Cytokine Production and Migration.
TL;DR: The expression of different specific S1P receptor profiles may provide a possibility to selectively influence M1- or M2-polarized macrophages.
Journal ArticleDOI
Sphingosine Kinase 2 and Ceramide Transport as Key Targets of the Natural Flavonoid Luteolin to Induce Apoptosis in Colon Cancer Cells
Loubna Abdel Hadi,Clara Di Vito,Giovanni Marfia,Anita Ferraretto,Cristina Tringali,Paola Viani,Laura Riboni +6 more
TL;DR: It is revealed for the first time that the dietary flavonoid luteolin exerts toxic effects on colon cancer cells by inhibiting both S1P biosynthesis and ceramide traffic, suggesting its dietary introduction/supplementation as a potential strategy to improve existing treatments in CRC.
Journal ArticleDOI
S1PR3 Signaling Drives Bacterial Killing and Is Required for Survival in Bacterial Sepsis.
Jinchao Hou,QiXing Chen,Xiaoliang Wu,DongYan Zhao,Hadas Reuveni,Tamar Licht,Menglong Xu,Hu Hu,Andreas Hoeft,Shmuel A. Ben-Sasson,Qiang Shu,Xiangming Fang +11 more
TL;DR: Higher levels of monocytic S1PR3 were associated with efficient intracellular bactericidal activity, better immune status, and preferable outcomes, and Interventions targeting S1 PR3 signaling could have translational implications for manipulating the innate immune response to combat pathogens.
Journal ArticleDOI
Downregulation of Critical Oncogenes by the Selective SK2 Inhibitor ABC294640 Hinders Prostate Cancer Progression.
TL;DR: Pre-clinical findings support the hypotheses that SK2 activity is required for prostate cancer function and that ABC294640 represents a new pharmacological agent for treatment of early stage and aggressive prostate cancer.
References
More filters
Journal ArticleDOI
STATs in cancer inflammation and immunity: a leading role for STAT3
TL;DR: Signal transducer and activator of transcription proteins are central in determining whether immune responses in the tumour microenvironment promote or inhibit cancer, and STAT3 is a promising target to redirect inflammation for cancer therapy.
Journal ArticleDOI
Principles of bioactive lipid signalling: lessons from sphingolipids
TL;DR: An understanding of the complex pathways of sphingolipid metabolism and the mechanisms that regulate lipid generation and lipid action is required to understand the mechanisms of cell growth, death, senescence, adhesion, migration, inflammation, angiogenesis and intracellular trafficking.
Journal ArticleDOI
The many roles of histone deacetylases in development and physiology: Implications for disease and therapy
TL;DR: In this article, the expression of many HDAC isoforms in eukaryotic cells raises questions about their possible specificity or redundancy, and whether they control global or specific programs of gene expression.
Journal Article
Heart-lung transplantation.
TL;DR: A broad overview of the various grounds upon which this difference is likely based and discuss recent advances in each area: 1) criteria for the selection of candidates and donors, 2) methods for ex-vivo preservation of donor organs, 3) technical execution of the operative procedure, and 4) prevention of postoperative infection as discussed by the authors.
Journal ArticleDOI
Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 Kinase
Liming Sun,Huayi Wang,Zhigao Wang,Sudan He,She Chen,Daohong Liao,Lai Wang,Jiacong Yan,Weilong Liu,Xiaoguang Lei,Xiaodong Wang +10 more
TL;DR: The identification of a small molecule called necrosulfonamide that specifically blocks necrosis downstream of RIP3 activation is reported, which implicate MLKL as a key mediator of necrosis signaling downstream of the kinase RIP3.