Fatty Acid Synthase (FASN), a cytoplasmic biosynthetic enzyme, is the major source of long-chain fatty acids, particularly palmitate. Caveolin-1 (Cav-1) is a palmitoylated lipid raft protein that plays a key role in signal transduction and cholesterol transport. Both proteins have been implicated in prostate cancer (PCa) progression, and Cav-1 regulates FASN expression in a mouse model of aggressive PCa. We demonstrate that FASN and Cav-1 are coordinately upregulated in human prostate tumors in a hormone-insensitive manner. Levels of FASN and Cav-1 protein expression discriminated between localized and metastatic cancers, and the two proteins exhibited analogous subcellular locations in a tumor subset. Endogenous FASN and Cav-1 were reciprocally co-immunoprecipitated from human and murine PCa cells, indicating that FASN forms a complex with Cav-1. FASN, a cytoplasmic enzyme, was induced to associate transiently with lipid raft membranes following alterations in signal transduction within the Src, Akt and EGFR pathways, suggesting that co-localization of FASN and Cav-1 is dependent on activation of upstream signaling mediators. A Cav-1 palmitoylation mutant, Cav-1(C133/143/156S), that prevents phosphorylation by Src, did not interact with FASN. When overexpressed in Cav-1-negative PCa cells, Cav-1(C133/143/156S) caused a reduction of both Src and Akt levels, as well as of their active, phosphorylated forms, in comparison with wild type Cav-1. These findings suggest that FASN and Cav-1 physically and functionally interact in PCa cells. They also imply that palmitoylation within this complex is involved in tumor growth and survival.
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Titolo: | Caveolin-1 interacts with a lipid raft-associated population of fatty acid synthase. | |
Autori: | D. D., Vizio; R. M., Adam; J., Kim; R., Kim; F., Sotgia; T., Williams; Demichelis, Francesca; K. R., Solomon; M., Loda; M. A., Rubin; M. P., Lisanti; M. R., Freeman | |
Autori Unitn: | ||
Titolo del periodico: | CELL CYCLE | |
Anno di pubblicazione: | 2008 | |
Codice identificativo Scopus: | 2-s2.0-47849132231 | |
Codice identificativo Pubmed: | 18635971 | |
Codice identificativo WOS: | WOS:000258829700025 | |
Handle: | http://hdl.handle.net/11572/88974 | |
Appare nelle tipologie: | 03.1 Articolo su rivista (Journal article) |