Fatty acid synthase causes drug resistance by inhibiting TNF-α and ceramide production

Hailan Liu, Xi Wu, Zizheng Dong, Zhiyong Luo, Zhenwen Zhao, Yan Xu, Jian Ting Zhang

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

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- production and nuclear factor-B activation as well as drug-induced activation of neutral sphingomyelinase. Thus, TNF-may play an important role in mediating FASN function in drug resistance.

Original languageEnglish (US)
Pages (from-to)776-785
Number of pages10
JournalJournal of Lipid Research
Volume54
Issue number3
DOIs
StatePublished - Mar 1 2013

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Keywords

  • Doxorubicin
  • Neutral sphingomyelinase
  • NK-kappa B
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

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