title: Fatty acid synthase drives the synthesis of phospholipids partitioning into detergent-resistant membrane microdomains.
abstract: Fatty acid synthase (FAS) is a key metabolic enzyme catalyzing the synthesis of long-chain saturated fatty acids. It plays a central role in the production of surfactant in fetal lungs, in the supply of fatty components of milk, and in the conversion and storage of energy in liver and adipose tissue. Remarkably high levels of FAS expression are found in the majority of human epithelial cancers. As the role of FAS in cancer cells remains largely unknown, we have initiated studies to assess the fate of newly synthesized lipids in cancer cells and have estimated the contribution of FAS to the synthesis of specific lipid classes by treating the cells with small interfering RNAs targeting FAS. Here, we show that in cancer cells FAS plays a major role in the synthesis of phospholipids partitioning into detergent-resistant membrane microdomains. These are raft-aggregates implicated in key cellular processes including signal transduction, intracellular trafficking, cell polarization, and cell migration. These findings reveal a novel role for FAS, provide important new insights into the otherwise poorly understood mechanisms underlying the control of lipid composition of membrane microdomains, and point to a link between FAS overexpression and dysregulation of membrane composition and functioning in tumor cells.
authors.affiliation: Laboratory for Experimental Medicine and Endocrinology (LEGENDO), University of Leuven, Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. Johan.Swinnen@med.kuleuven.ac.be
authors.forename: Johannes V
authors.initials: JV
authors.lastname: Swinnen
authors.forename: Paul P
authors.initials: PP
authors.lastname: Van Veldhoven
authors.forename: Leen
authors.initials: L
authors.lastname: Timmermans
authors.forename: Ellen
authors.initials: E
authors.lastname: De Schrijver
authors.forename: Koen
authors.initials: K
authors.lastname: Brusselmans
authors.forename: Frank
authors.initials: F
authors.lastname: Vanderhoydonc
authors.forename: Tine
authors.initials: T
authors.lastname: Van de Sande
authors.forename: Hannelore
authors.initials: H
authors.lastname: Heemers
authors.forename: Walter
authors.initials: W
authors.lastname: Heyns
authors.forename: Guido
authors.initials: G
authors.lastname: Verhoeven
mesh_terms: D003902:Detergents / Q000737:chemistry*; D015536:Down-Regulation / Q000502:physiology; D064429:Fatty Acid Synthases / Q000378:metabolism*; D006801:Humans; D008297:Male; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D011471:Prostatic Neoplasms; D034741:RNA, Small Interfering / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D003902:Detergents; D010743:Phospholipids; D034741:RNA, Small Interfering; D064429:Fatty Acid Synthases