| 项目编号 |
PRJCA049522 |
| 项目标题 |
LPE18:1 drives clear cell renal cell carcinoma by stabilizing SIRT6 to reprogram lipid metabolism |
| 涉及领域 |
Medical |
| 数据类型 |
Transcriptome or Gene expression
Raw sequence reads
Proteome
Metabonomics
|
| 物种名称 |
|
| 描述信息 |
Clear cell renal cell carcinoma (ccRCC) is characterized by profound lipid metabolic dysregulation, yet the mechanisms linking peritumoral adipose tissue (PAT)-derived lipid metabolites to tumor aggressiveness remain poorly defined. Here, we identified lysophosphatidylethanolamine 18:1 (LPE18:1), a lipid metabolite enriched in PAT and the arterial blood of ccRCC patients, as a critical driver of tumor growth and lipid deposition. Through multiomics analyses and functional studies, we demonstrated that LPE18:1 upregulates F-actin-capping protein subunit alpha-1 (CAPZA1), which recruits ubiquitin-specific peptidase 48 (USP48) to stabilize the NAD-dependent protein deacetylase sirtuin-6 (SIRT6) by inhibiting its proteasomal degradation.Increased SIRT6 epigenetically promotes acetyl-CoA acetyltransferase 2 (ACAT2) expression, redirecting lipid metabolism toward free cholesterol accumulatio-a hallmark of ccRCC aggressiveness. Clinically, CAPZA1 and SIRT6 levels correlate with advanced tumor stage and poor prognosis in ccRCC cohorts. Genetic or pharmacological inhibition of the CAPZA1/SIRT6 axis can reverse LPE18:1-induced lipid deposition and tumor progression in xenograft models. Notably, 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. |
| 样品范围 |
Multiisolate |
| 发布日期 |
2026-01-15 |
| 出版信息 |
| PubMed ID |
文章标题 |
杂志名称 |
Doi |
发表年份 |
| 41354870
|
Lysophosphatidylethanolamine 18: 1 drives clear cell renal cell carcinoma by stabilizing SIRT6 to reprogram lipid metabolism
|
Signal Transduction and Targeted Therapy
|
10.1038/s41392-025-02496-1
|
2025
|
|
|
| 项目资金来源 |
| 机构 |
项目类型 |
授权项目ID |
授权项目名称 |
| National Natural Science Foundation of China (NSFC)
|
|
82472667
|
|
|
|
| 提交者 |
Zhan
Yang (yangzhan@hebmu.edu.cn)
|
| 提交单位 |
The Affiliated Hospital of Qingdao University |
| 提交日期 |
2025-10-28 |
