| 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
|
| リソース情報 |
| ヒト・動物細胞 |
MKN45(RCB1001) |
