Abstract
Tumor metastasis remains one of the major causes of cancer‐related deaths in patients with solid tumors. Mechanisms by which metabolic alterations regarding pro‐survival lipid signaling activation in inducing cancer cell migration and metastasis are largely unknown. Here, we demonstrate that sphingosine 1‐phosphate (S1P) metabolism activates endogenous complement signaling for inducing tumor metastasis via inducing inflammasome‐mediated pro‐inflammation. Our studies using molecular, pharmacologic, and genetic tools showed that activation of S1P and S1P receptor 1 (S1P/S1PR1) induces tumor metastasis via enhanced intracellular complement signaling by the regulation of the C3‐PPIL1 complex and subsequent inflammasome activation in cancer cells and in vivo xenograft‐derived tumors.
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