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.

Citation Format: Alhaji H. Janneh, Besim Ogretmen. Pro-survival lipid metabolism activates intracellular complement signaling to induce inflammasome-mediated tumor metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1312.