文章基本信息

标题：Fatty acid synthase causes drug resistance by inhibiting TNF-α and ceramide production
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作者：Hailan Liu ; Xi Wu ; Zizheng Dong 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2013
卷号：54
期号：3
页码：776-785
DOI：10.1194/jlr.M033811
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Fatty acid synthase (FASN) is a key enzyme in the synthesis of palmitate, the precursor of major nutritional, energetic, and signaling lipids. FASN expression is upregulated in many human cancers and appears to be important for cancer cell survival. Overexpression of FASN has also been found to associate with poor prognosis and higher risk of recurrence of human cancers. Indeed, elevated FASN expression has been shown to contribute to drug resistance. However, the mechanism of FASN-mediated drug resistance is currently unknown. In this study, we show that FASN overexpression causes resistance to multiple anticancer drugs via inhibiting drug-induced ceramide production, caspase 8 activation, and apoptosis. We also show that FASN overexpression suppresses tumor necrosis factor-α production and nuclear factor-κB activation as well as drug-induced activation of neutral sphingomyelinase. Thus, TNF-α may play an important role in mediating FASN function in drug resistance.
关键词：tumor necrosis factor ; NK-kappa B ; neutral sphingomyelinase ; doxorubicin