Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond
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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
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Sphingosine 1-phosphate regulates IL-8 expression and secretion via S1PR1 and S1PR2 receptors-mediated signaling in extravillous trophoblast derived HTR-8/SVneo cells.
TL;DR: S1P induces IL-8 gene expression and protein secretion in EVT derived HTR-8/SVneo cells but not in BeWo cells for the first time, and rho GTPases signaling is essential for S1P-inducedIL-8 secretion.
Journal ArticleDOI
A bidirectional crosstalk between glioblastoma and brain endothelial cells potentiates the angiogenic and proliferative signaling of sphingosine-1-phosphate in the glioblastoma microenvironment.
Loubna Abdel Hadi,V. Anelli,Laura Guarnaccia,Stefania Elena Navone,Matteo Beretta,Francesco Moccia,Cristina Tringali,Vasile Urechie,Rolando Campanella,Giovanni Marfia,Laura Riboni +10 more
TL;DR: The results envision glioblastoma-endothelial crosstalk as a multi-compartmental strategy to enforce pro-tumoral sphingosine-1-phosphate signaling in the gliOBlastoma microenvironment.
Journal ArticleDOI
Sphingosine-1-Phosphate Receptor-1 Promotes Environment-Mediated and Acquired Chemoresistance
Veronica Lifshitz,Saul J. Priceman,Wenzhao Li,Gregory Cherryholmes,Heehyoung Lee,Adar Makovski-Silverstein,Lucia Borriello,Yves A. DeClerck,Yves A. DeClerck,Hua Yu +9 more
TL;DR: In vitro and in human NB xenograft models, treatment with FTY720, an FDA-approved drug and antagonist of S1PR1, dramatically sensitizes drug-resistant cells to etoposide and is identified as a critical target for reducing both EMDR and acquired chemoresistance in NB.
Journal ArticleDOI
Syntheses and in vitro evaluation of new S1PR1 compounds and initial evaluation of a lead F-18 radiotracer in rodents.
TL;DR: Ex-vivo autoradiography and initial biodistribution studies in rodents were performed, suggesting that [18F]12b has potential to be an F-18 labeled radiotracer for imaging S1PR1 in the brain of the animal in vivo.
Journal ArticleDOI
Soy Protein Isolate Protects Against Ethanol-Mediated Tumor Progression in Diethylnitrosamine-Treated Male Mice
Kelly E. Mercer,Casey F. Pulliam,Leah Hennings,Keith Lai,Mario A. Cleves,E. Ellen Jones,Richard R. Drake,Martin J. J. Ronis +7 more
TL;DR: It is concluded that soy prevents tumorigenesis by reducing proinflammatory and oxidative environment resulting from EtOH-induced hepatic injury, and by reducing hepatocyte proliferation through inhibition of β-catenin signaling, which may involve changes in sphingolipid signaling.
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