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| Status |
Public on Mar 11, 2025 |
| Title |
TRAF3 loss protects glioblastoma cells from lipid peroxidation and immune elimination via dysregulated lipid metabolism |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Glioblastoma (GBM) is a highly aggressive form of brain tumor characterized by dysregulated metabolism. Increased fatty acid oxidation (FAO) protects tumor cells from lipid peroxidation-induced cell death, although the precise mechanisms involved remain unclear. Herein, we report that loss of tumor necrosis factor receptor-associated factor 3 (TRAF3) in GBM critically regulates lipid peroxidation and tumorigenesis by controlling the oxidation of polyunsaturated fatty acids (PUFAs). TRAF3 is frequently repressed in GBM due to promoter hypermethylation. TRAF3 interacts with enoyl-CoA hydratase 1 (ECH1), an enzyme catalyzing the isomerization of unsaturated fatty acids (UFAs), and mediates K63-linked ubiquitination of ECH1 at Lys214. ECH1 ubiquitination impedes TOMM20-dependent mitochondrial translocation of ECH1, which otherwise promotes the oxidation of UFAs, preferentially the PUFAs, and limits lipid peroxidation. Overexpression of TRAF3 enhances the sensitivity of GBM to ferroptosis and anti-PD-L1 immunotherapy in mice. Thus, the TRAF3-ECH1 axis plays a key role in the metabolism of PUFAs, and is crucial for lipid peroxidation damage and immune elimination in GBM.
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| Overall design |
RNA-seq profiling of patient-derived GBM0709 cells stably transfected with TRAF3 overexpression lentivirus or the control lentivirus.
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| Contributor(s) |
Zeng Y, Zhao L, Zeng K, Deng F, Bai X, Song Y, Zhou A |
| Citation missing |
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| Submission date |
Jan 06, 2025 |
| Last update date |
Mar 11, 2025 |
| Contact name |
Aidong Zhou |
| E-mail(s) |
aidern0927@smu.edu.cn
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| Organization name |
Southern Medical University
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| Department |
Department of Cell Biology
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| Lab |
Zhou Aidong
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| Street address |
Shatai North Road
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| City |
Guangzhou |
| State/province |
Guangdong |
| ZIP/Postal code |
510515 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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