論文 - 詳細
| RRC ID | 66846 |
|---|---|
| 著者 | Yoshino H, Sato Y, Nakano M. |
| タイトル | KPNB1 Inhibitor Importazole Reduces Ionizing Radiation-Increased Cell Surface PD-L1 Expression by Modulating Expression and Nuclear Import of IRF1. |
| ジャーナル | Curr Issues Mol Biol |
| Abstract |
Programmed death-ligand 1 (PD-L1) is an immune checkpoint molecule that negatively regulates anti-tumor immunity. Recent reports indicate that anti-cancer treatments, such as radiation therapy, increase PD-L1 expression on the surface of tumor cells. We previously reported that the nuclear transport receptor karyopherin-β1 (KPNB1) is involved in radiation-increased PD-L1 expression on head-and-neck squamous cell carcinoma cells. However, the mechanisms underlying KPNB1-mediated, radiation-increased PD-L1 expression remain unknown. Thus, the mechanisms of radiation-increased, KPNB1-mediated PD-L1 expression were investigated by focusing on the transcription factor interferon regulatory factor 1 (IRF1), which is reported to regulate PD-L1 expression. Western blot analysis showed that radiation increased IRF1 expression. In addition, flow cytometry showed that IRF1 knockdown decreased cell surface PD-L1 expression of irradiated cells but had a limited effect on non-irradiated cells. These findings suggest that the upregulation of IRF1 after irradiation is required for radiation-increased PD-L1 expression. Notably, immunofluorescence and western blot analyses revealed that KPNB1 inhibitor importazole not only diffused nuclear localization of IRF1 but also decreased IRF1 upregulation by irradiation, which attenuated radiation-increased PD-L1 expression. Taken together, these findings suggest that KPNB1 mediates radiation-increased cell surface PD-L1 expression through both upregulation and nuclear import of IRF1. |
| 巻・号 | 43(1) |
| ページ | 153-162 |
| 公開日 | 2021-5-19 |
| DOI | 10.3390/cimb43010013 |
| PII | cimb43010013 |
| PMID | 34069326 |
| PMC | PMC8929148 |
| MeSH | Active Transport, Cell Nucleus B7-H1 Antigen / antagonists & inhibitors* Cell Line, Tumor Gene Expression Regulation, Neoplastic / drug effects* Humans Immunotherapy / methods Interferon Regulatory Factor-1 / antagonists & inhibitors* Interferon Regulatory Factor-1 / genetics Interferon Regulatory Factor-1 / metabolism Lung Neoplasms / drug therapy Lung Neoplasms / metabolism* Lung Neoplasms / pathology Lung Neoplasms / radiotherapy Quinazolines / pharmacology* Radiation, Ionizing beta Karyopherins / antagonists & inhibitors* |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | A549 |