| 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 | Proteomic 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 | 2025-10-29 |
HTTP download speed may be slow. It is highly recommended that you download the dataset using a dedicated FTP tool (such as FileZilla Client).
| File ID | File Title | Number/Samples | File Type | File Size | File Suffix | Download |
|---|---|---|---|---|---|---|
| OMIX012596-01 | shCON | 3 | Proteomic Data by Mass Spectrometry (MS) | 4.51 GB | tar | Controlled |
| OMIX012596-02 | shCAPZA1 | 3 | Proteomic Data by Mass Spectrometry (MS) | 4.57 GB | tar | Controlled |
| Paper Title | Journal Name | Publish Time | Accession | Citing Type |
|---|---|---|---|---|
| Lysophosphatidylethanolamine 18: 1 drives clear cell renal cell carcinoma by stabilizing SIRT6 to reprogram lipid metabolism | Signal Transduction and Targeted Therapy | 2025-12 | OMIX012675 OMIX012656 OMIX012596 | Deposit |