論文 - 詳細
| RRC ID | 83335 |
|---|---|
| 著者 | Xu Y, Qian X, Cai G, Lin Z, Huang W, Wang C, Wu H, Zhang Y, Sun J, Zhang Q. |
| タイトル | WTX-L/β-arrestin2/LCN2 axis controls vulnerability to ferroptosis in gastric cancer. |
| ジャーナル | iScience |
| Abstract |
Gastric cancer (GC) is one of the most prevalent and lethal cancers worldwide. Ferroptosis is a form of iron-dependent regulated cell death emerging as a promising strategy for cancer therapy, whereas the regulation mechanism remains unclear. WTX has been recognized as a potential tumor suppressor, but attempts at targeted therapy have not achieved substantial progress. Further research into the structure, function, and mechanisms is urgently needed. Herein, we identified a long isoform of WTX (WTX-L) as a potent ferroptosis effector in GC. Mechanistically, WTX-L competitively interacts with β-arrestin2, disrupting its direct binding to IκBα and subsequently activating the NF-κB/LCN2 pathway. LCN2 further triggers ferroptosis by significantly increasing the labile Fe2+ pool and promoting excessive lipid peroxidation. Blockade of the WTX-L/β-arrestin2/NF-κB/LCN2 axis significantly diminished the activity of ferroptosis inducers (erastin and RSL3) in vivo. Collectively, these findings reveal that targeting the ferroptosis vulnerabilities through WTX-L may represent a promising strategy for GC. |
| 巻・号 | 28(3) |
| ページ | 111964 |
| 公開日 | 2025-3-21 |
| DOI | 10.1016/j.isci.2025.111964 |
| PII | S2589-0042(25)00224-X |
| PMID | 40109379 |
| PMC | PMC11919608 |
| IF | 4.447 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | |
| 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 | MKN45(RCB1001) |