Radiation-induced IL-1β expression and secretion promote cancer cell migration/invasion via activation of the NF-κB-RIP1 pathway
| Autor: | Jong Kuk Park, Jae-Sung Kim, Jin-Hee Kwon, Jeong Hyun Cho, Na-Gyeong Lee, Jie-Young Song, Hong-Duck Um, Aram Kang, Sang-Gu Hwang, Sang Cheul Oh, In Su Jung |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Lung Neoplasms Interleukin-1beta Biophysics Biochemistry Metastasis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Cell Movement Radiation Ionizing medicine Animals Humans Secretion Neoplasm Invasiveness Autocrine signalling Receptor Molecular Biology Mice Inbred BALB C Antagonist NF-kappa B RNA-Binding Proteins NF-κB Cell Biology medicine.disease Cell biology Up-Regulation Nuclear Pore Complex Proteins 030104 developmental biology chemistry A549 Cells Gamma Rays 030220 oncology & carcinogenesis Signal transduction Signal Transduction |
| Zdroj: | Biochemical and biophysical research communications. 534 |
| ISSN: | 1090-2104 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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