Fatty acid synthase drives the synthesis of phospholipids partitioning into detergent-resistant membrane microdomains
Fatty acid synthase drives the synthesis of phospholipids partitioning into detergent-resistant membrane microdomains
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DOI：
10.1016/s0006-291x(03)00265-1
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发表时间：
2003-03-21
影响因子：
3.1
通讯作者：
Verhoeven, G
中科院分区：
文献类型：
--
作者：
Swinnen, JV;Van Veldhoven, PP;Verhoeven, G
脂肪酸合成酶（FAS）是催化长链饱和脂肪酸合成的关键代谢酶。它在胎肺中表面活性剂的产生、乳汁中脂肪成分的供应以及肝脏和脂肪组织中能量的转换和储存中起着核心作用。在大多数人类上皮癌中发现了显著高水平的FAS表达。由于FAS在癌细胞中的作用在很大程度上仍然未知，我们已经启动了研究，以评估癌细胞中新合成的脂质的命运，并通过用靶向FAS的小干扰RNA处理细胞来估计FAS对特定脂质类合成的贡献。在这里，我们表明，在癌细胞中FAS起着重要的作用，在合成的磷脂分配到洗涤剂耐膜微区。这些是涉及关键细胞过程的筏聚集体，包括信号转导、细胞内运输、细胞极化和细胞迁移。这些发现揭示了FAS的一个新的作用，提供了重要的新的见解，否则知之甚少的机制控制膜微区的脂质组成，并指出FAS过度表达和失调的膜组成和功能在肿瘤细胞之间的联系。(C)2003 Elsevier Science（美国）。All rights reserved.
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. (C) 2003 Elsevier Science (USA). All rights reserved.