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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New insights into functions of the sphingosine-1-phosphate transporter SPNS2
TL;DR: Recent advances in understanding the physiological actions of SPNS2 in regulating levels of S1P and the S1p gradient that exists between the high circulating concentrations of S 1P and low tissue levels that control lymphocyte trafficking are discussed.
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Targeting Sphingosine-1-Phosphate Signaling in Immune-Mediated Diseases: Beyond Multiple Sclerosis.
TL;DR: The S1P-S1PR pathway is involved in the pathogenesis of several cellular and physiological events, including lymphocyte/hematopoietic cell trafficking as discussed by the authors.
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Sphingosine 1-phosphate signaling in bone remodeling: multifaceted roles and therapeutic potential
TL;DR: The progress made in bone research is summarized and analyzed in the context of the current knowledge of sphingolipid-related mechanisms regulating bone remodeling, with particular emphasis given to bioactive sphingosine 1-phosphate and S1P receptors.
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T cell-intrinsic S1PR1 regulates endogenous effector T-cell egress dynamics from lymph nodes during infection.
Alexandre P. Benechet,Manisha Menon,Daqi Xu,Tasleem Samji,Leigh Maher,Thomas T. Murooka,Thorsten R. Mempel,Brian S. Sheridan,François M. Lemoine,Kamal M. Khanna +9 more
TL;DR: It is demonstrated that, even when LN retention signals such as CC chemokine receptor 7 (CCR7) are down-regulated, T cell intrinsic S1PR1 is the master regulator of effector T-cell emigration from the dLN.
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The Regulation of NRF2 by Nutrient-Responsive Signaling and Its Role in Anabolic Cancer Metabolism.
TL;DR: How theNRF2-KEAP1 signaling pathway is altered in cancer, how NRF2 is regulated by changes in cellular metaboli is described and recent exciting findings demonstrate a role for NRF 2-mediated metabolic deregulation that supports cancer cell proliferation.
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