Radiation-induced IL-1β expression and secretion promote cancer cell migration/invasion via activation of the NF-κB–RIP1 pathway.

Here, we demonstrate that interleukin-1β (IL-1β) contributes to the γ-ionizing radiation (IR)-induced increase of migration/invasion in A549 lung cancer cells, and that this occurs via RIP1 upregulation. We initially observed that the protein expression and secreted concentration of IL-1β were increased upon exposure of A549 cells to IR. We then demonstrated that IR-induced IL-1β is located downstream of the NF-κB–RIP1 signaling pathway. Treatments with siRNA and specific pharmaceutical inhibitors of RIP1 and NF-κB suppressed the IR-induced increases in the protein expression and secreted concentration of IL-1β. IL-1Ra, an antagonist of IL-1β, treatment suppressed the IR-induced epithelial-mesenchymal transition (EMT) and IR-induced invasion/migration in vitro. These results suggest that IL-1β could regulate IR-induced EMT. We also found that IR could induce the expression of IL-1β expression in vivo and that of IL-1 receptor (R) I/II in vitro and in vivo. The IR-induced increases in the protein levels of IL-1 RI/II and IL-1β suggest that an autocrine loop between IL-1β and IL-1 RI/II might play important roles in IR-induced EMT and migration/invasion. Based on these collective results, we propose that IR concomitantly activates NF-κB and RIP1 to trigger the NF-κB–RIP1–IL-1β–IL-1RI/II–EMT pathway, ultimately promoting metastasis. • We found γ-ionizing radiation (IR) induces IL-1β expression and secretion. • NF-κB and RIP1 regulate the IR-induced upregulation and secretion of IL-1β. • IR-induced IL-1β promotes cancer cell migration and invasion via EMT induction. • IR induces expressions of IL-1β and its receptors, IL-1RI/II, in vitro and in vivo. • We validated new signaling pathway: IR–RIP1–NF-κB–IL-1β–IL-1β receptor I/II–EMT signaling. [ABSTRACT FROM AUTHOR]