Caveolin-1-mediated sphingolipid oncometabolism underlies a metabolic vulnerability of prostate cancer.

ABSTRACT: Plasma and tumor caveolin-1 (Cav-1) are linked with disease progression in prostate cancer. Here we report that metabolomic profiling of longitudinal plasmas from a prospective cohort of 491 active surveillance (AS) participants indicates prominent elevations in plasma sphingolipids in AS progressors that, together with plasma Cav-1, yield a prognostic signature for disease progression. Mechanistic studies of the underlying tumor supportive onco-metabolism reveal coordinated activities through which Cav-1 enables rewiring of cancer cell lipid metabolism towards a program of 1) exogenous sphingolipid scavenging independent of cholesterol, 2) increased cancer cell catabolism of sphingomyelins to ceramide derivatives and 3) altered ceramide metabolism that results in increased glycosphingolip

SUBMITTER: Vykoukal J 

PROVIDER: S-EPMC7453025 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature