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

26 Citations (Scopus)

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

Fingerprint

Fatty Acid Synthases
Ceramides
Drug Resistance
Pharmaceutical Preparations
Chemical activation
Sphingomyelin Phosphodiesterase
Neoplasms
Caspase 8
Palmitates
Cell Survival
Tumor Necrosis Factor-alpha
Cells
Apoptosis
Lipids
Recurrence
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

Cite this

Fatty acid synthase causes drug resistance by inhibiting TNF-α and ceramide production. / Liu, Hailan; Wu, Xi; Dong, Zizheng; Luo, Zhiyong; Zhao, Zhenwen; Xu, Yan; Zhang, Jian-Ting.

In: Journal of Lipid Research, Vol. 54, No. 3, 03.2013, p. 776-785.

Research output: Contribution to journalArticle

Liu, Hailan ; Wu, Xi ; Dong, Zizheng ; Luo, Zhiyong ; Zhao, Zhenwen ; Xu, Yan ; Zhang, Jian-Ting. / Fatty acid synthase causes drug resistance by inhibiting TNF-α and ceramide production. In: Journal of Lipid Research. 2013 ; Vol. 54, No. 3. pp. 776-785.
@article{910ea7ae6f854f32aeb6fe9338b41113,
title = "Fatty acid synthase causes drug resistance by inhibiting TNF-α and ceramide production",
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.",
keywords = "Doxorubicin, Neutral sphingomyelinase, NK-kappa B, Tumor necrosis factor",
author = "Hailan Liu and Xi Wu and Zizheng Dong and Zhiyong Luo and Zhenwen Zhao and Yan Xu and Jian-Ting Zhang",
year = "2013",
month = "3",
doi = "10.1194/jlr.M033811",
language = "English",
volume = "54",
pages = "776--785",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "3",

}

TY - JOUR

T1 - Fatty acid synthase causes drug resistance by inhibiting TNF-α and ceramide production

AU - Liu, Hailan

AU - Wu, Xi

AU - Dong, Zizheng

AU - Luo, Zhiyong

AU - Zhao, Zhenwen

AU - Xu, Yan

AU - Zhang, Jian-Ting

PY - 2013/3

Y1 - 2013/3

N2 - 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.

AB - 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.

KW - Doxorubicin

KW - Neutral sphingomyelinase

KW - NK-kappa B

KW - Tumor necrosis factor

UR - http://www.scopus.com/inward/record.url?scp=84874027191&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84874027191&partnerID=8YFLogxK

U2 - 10.1194/jlr.M033811

DO - 10.1194/jlr.M033811

M3 - Article

VL - 54

SP - 776

EP - 785

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

IS - 3

ER -