An autocrine sphingosine-1-phosphate signaling loop enhances NF-κB-activation and survival
1 Department of Biology, Åbo Akademi University, 20520 Turku, Finland
2 Department of Biochemistry and Pharmacy, Åbo Akademi University, 20520 Turku, Finland
3 Turku Centre for Biotechnology, Åbo Akademi University & University of Turku, 20520 Turku, Finland
4 The Minerva Foundation Institute for Medical Research, 00290 Helsinki, Finland
5 Current Address: Institute of Biomedicine, University of Helsinki, 00290 Helsinki, Finland
6 Current Address: Breakthrough Toby Robbins Breast Cancer Research Centre, Institute of Cancer Research, London SW3 6JB, UK
BMC Cell Biology 2010, 11:45 doi:10.1186/1471-2121-11-45Published: 24 June 2010
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-κB dependent manner. NF-κB 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-κB activation.
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.