Reference - Detail
| RRC ID | 83335 |
|---|---|
| Author | Xu Y, Qian X, Cai G, Lin Z, Huang W, Wang C, Wu H, Zhang Y, Sun J, Zhang Q. |
| Title | WTX-L/β-arrestin2/LCN2 axis controls vulnerability to ferroptosis in gastric cancer. |
| Journal | 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. |
| Volume | 28(3) |
| Pages | 111964 |
| Published | 2025-3-21 |
| DOI | 10.1016/j.isci.2025.111964 |
| PII | S2589-0042(25)00224-X |
| PMID | 40109379 |
| PMC | PMC11919608 |
| IF | 4.447 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | MKN45(RCB1001) |