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Crosstalk between pro-survival sphingolipid metabolism and complement signaling induces inflammasome-mediated tumor metastasis

Cell Reports. 2022-12; 
Alhaji H. Janneh, Mohamed Faisal Kassir, F. Cansu Atilgan, Stephen Tomlinson, Shikhar Mehrotra, Besim Ogretmen
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摘要

Crosstalk between metabolic and signaling events that induce tumor metastasis remains elusive. Here, we determine how oncogenic sphingosine 1-phosphate (S1P) metabolism induces intracellular C3 complement activation to enhance migration/metastasis. We demonstrate that increased S1P metabolism activates C3 complement processing through S1P receptor 1 (S1PR1). S1P/S1PR1-activated intracellular C3b-a0 2 is associated with PPIL1 through glutamic acid 156 (E156) and aspartic acid 111 (D111) residues, resulting in NLRP3/ inflammasome induction. Inactivation mutations of S1PR1 to prevent S1P signaling or mutations of C3b-a0 2 to prevent its association with PPIL1 attenuate inflammasome activation and reduce lun... More

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