Longevity & AgingFat Tissue Lipid Fuels Kidney Cancer Growth Through a Novel Metabolic Signaling Chain
Researchers discovered that lysophosphatidylethanolamine 18:1 (LPE18:1), produced by browning perinephric adipose tissue surrounding kidney tumors, is avidly consumed by clear cell renal cell carcinoma (ccRCC) cells to fuel their growth. LPE18:1 elevates CAPZA1, which recruits the deubiquitinase USP48 to stabilize the epigenetic regulator SIRT6, preventing its proteasomal breakdown. Stabilized SIRT6 then promotes expression of ACAT2, redirecting metabolism toward free cholesterol accumulation—a defining hallmark of ccRCC. Blocking this axis with genetic tools or the SIRT6 inhibitor OSS-128167 suppressed tumor growth in xenograft models, pointing to CAPZA1 and SIRT6 as actionable drug targets in this aggressive kidney cancer subtype.
