Caveolin-1 interacts with a lipid raft-associated population of fatty acid synthase.
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.
Mesh Terms:
Animals, Caveolin 1, Cell Line, Tumor, Enzyme Activation, Fatty Acid Synthases, Humans, Male, Membrane Microdomains, Mice, Mutation, Palmitic Acid, Phosphatidylinositol 3-Kinases, Prostate, Prostatic Neoplasms, Protein Binding, Protein Kinase Inhibitors, Protein Transport, Proto-Oncogene Proteins pp60(c-src), Signal Transduction
Animals, Caveolin 1, Cell Line, Tumor, Enzyme Activation, Fatty Acid Synthases, Humans, Male, Membrane Microdomains, Mice, Mutation, Palmitic Acid, Phosphatidylinositol 3-Kinases, Prostate, Prostatic Neoplasms, Protein Binding, Protein Kinase Inhibitors, Protein Transport, Proto-Oncogene Proteins pp60(c-src), Signal Transduction
Cell Cycle
Date: Jul. 15, 2008
PubMed ID: 18635971
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