| Title |
LPE18:1 drives clear cell renal cell carcinoma by stabilizing SIRT6 to reprogram lipid metabolism |
| Description |
ccRCC is characterized by profound lipid metabolic dysregulation, yet the mechanisms linking peritumoral PAT-derived lipid metabolites to tumor aggressiveness remain poorly defined. We identified LPE18:1, as a critical driver of tumor growth and lipid deposition. We demonstrated that LPE18:1 upregulates CAPZA1, which recruits USP48 to stabilize the SIRT6 . Increased SIRT6 epigenetically promotes ACAT2 expression, redirecting lipid metabolism toward free cholesterol accumulation-a hallmark of ccRCC aggressiveness. Genetic or pharmacological inhibition of the CAPZA1/SIRT6 axis can reverse LPE18:1-induced lipid deposition and tumor progression in xenograft models. Targeting this axis with the SIRT6 inhibitor OSS-128167 combined with CAPZA1 depletion significantly suppressed ccRCC cell growth. Our study reveals a PAT-derived lipid metabolite-fuelled signaling cascade that reprograms lipid metabolism in ccRCC, identifying CAPZA1/USP48/SIRT6 as actionable therapeutic targets for metabolic malignancies. |
| Organism |
Homo sapiens |
| Data Type |
Metabolome Data by Mass Spectrometry (MS) |
| Data Accessibility |
Controlled-access |
| BioProject |
PRJCA049522 |
| Release Date |
2026-01-02 |
| Submitter |
Zhan Yang (yangzhan@hebmu.edu.cn) |
| Organization |
The Affiliated Hospital of Qingdao University |
| Submission Date |
2025-10-30 |