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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Adaptor Proteins, Signal Transducing, Autocrine Communication, Calcium-Calmodulin-Dependent Protein Kinases, Cell Line, Tumor, Cell Survival, Enzyme Activation, Fas Ligand Protein, Feedback, Physiological, Flavonoids, Humans, Lysophospholipids, NF-kappa B, Pyrazoles, Pyridines, RNA, Small Interfering, Receptors, Lysosphingolipid, Signal Transduction, Sphingosine, Transgenes.
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Does an autocrine sphingosine-1-phosphate signaling loop enhance NF-kappaB-activation and survival? Context: Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates a multitude of cellular functions, including cell proliferation, survival, migration and angiogenesis. S1P mediates its effects either by signaling through G protein-coupled receptors (GPCRs) or through an intracellular mode of action. In this study, we have investigated the mechanism behind S1P-induced survival signalling. We found that S1P protected cells from FasL-induced cell death in an NF-kappaB dependent manner. NF-kappaB was activated by extracellular S1P via S1P2 receptors and Gi protein signaling. Our study also demonstrates that extracellular S1P stimulates cells to rapidly produce and secrete additional S1P, which can further amplify the NF-kappaB activation.
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We propose a self-amplifying loop of autocrine S1P with capacity to enhance cell survival. The mechanism provides increased understanding of the multifaceted roles of S1P in regulating cell fate during normal development and carcinogenesis. Final Decision: yes