Fatty acid synthase plays a role in cancer metabolism beyond providing fatty acids for phospholipid synthesis or sustaining elevations in glycolytic activity

Hopperton, Kathryn E.; Duncan, Robin E.; Bazinet, Richard P.; Archer, Michael C.

doi:10.1016/j.yexcr.2013.10.016

Cited by 78 publications

(63 citation statements)

References 33 publications

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“…The co-occurrence of the Warburg effect and lipogenesis has been demonstrated in several cancer/tumor cells (Menendez and Lupu, 2007;Vander Heiden et al, 2009;Baenke et al, 2013;Mashima et al, 2009;Hopperton et al, 2014) and in cultured mammalian cells infected by vertebrate viruses (Munger et al, 2008;Delgado et al, 2012;Diamond et al, 2010). For example, in Kaposi's sarcoma-associated herpesvirus (KHSV)-infected cells, over 50% of the LCFAs were significantly increased, while no LCFA was decreased (Delgado et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Since fatty acid synthase (FAS) is known to regulate lipogenesis in cancer/tumor cells (Menendez and Lupu, 2007;Mashima et al, 2009;Furuta et al, 2008;Flavin et al, 2010;Hopperton et al, 2014) and in cells with an oncogenic viral infection (Kim et al, 2008;Syed et al, 2010;Wang et al, 2010;Delgado et al, 2012), we next investigated whether this important enzyme might also be involved in lipogenesis during WSSV infection as well as how it might be regulated. Fig.…”

Section: Wssv Induces Fas Expression Through the Pi3k-akt-mtorhif1a Smentioning

confidence: 99%

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To complete its replication cycle, a shrimp virus changes the population of long chain fatty acids during infection via the PI3K-Akt-mTOR-HIF1α pathway

Hsieh

Chen

et al. 2015

Developmental & Comparative Immunology

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Section: Discussionmentioning

confidence: 99%

Section: Wssv Induces Fas Expression Through the Pi3k-akt-mtorhif1a Smentioning

confidence: 99%

To complete its replication cycle, a shrimp virus changes the population of long chain fatty acids during infection via the PI3K-Akt-mTOR-HIF1α pathway

Hsieh

Chen

et al. 2015

Developmental & Comparative Immunology

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“…Both MCF7 and Panc-1 cells are known to express high levels of endogenous FASN, and M3K cells have further elevated endogenous FASN (2,8,16). To eliminate the possibility that the above observations may be due to forced increases in FASN expression either by ectopic transfection or drug selection, we transiently knocked down FASN in the parental MCF7 cells and tested its effect on doxorubicin sensitivity, NHEJ activity, and PARP-1 expression.…”

Section: Fasn Overexpression Promotes Parp-1 Expression Which Mediatmentioning

confidence: 99%

FASN regulates cellular response to genotoxic treatments by increasing PARP-1 expression and DNA repair activity via NF-κB and SP1

Dong

Wang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Fatty acid synthase (FASN), the sole cytosolic mammalian enzyme for de novo lipid synthesis, is crucial for cancer cell survival and associates with poor prognosis. FASN overexpression has been found to cause resistance to genotoxic insults. Here we tested the hypothesis that FASN regulates DNA repair to facilitate survival against genotoxic insults and found that FASN suppresses NF-κB but increases specificity protein 1 (SP1) expression. NF-κB and SP1 bind to a composite element in the poly(ADP-ribose) polymerase 1 (PARP-1) promoter in a mutually exclusive manner and regulate PARP-1 expression. Up-regulation of PARP-1 by FASN in turn increases Ku protein recruitment and DNA repair. Furthermore, lipid deprivation suppresses SP1 expression, which is able to be rescued by palmitate supplementation. However, lipid deprivation or palmitate supplementation has no effect on NF-κB expression. Thus, FASN may regulate NF-κB and SP1 expression using different mechanisms. Altogether, we conclude that FASN regulates cellular response against genotoxic insults by up-regulating PARP-1 and DNA repair via NF-κB and SP1.fatty acid synthase | transcription regulation | DNA repair | drug resistance | radiation resistance F atty acid synthase (FASN) is the key mammalian enzyme required for de novo synthesis of palmitate. FASN expression and activity are largely suppressed by sufficient dietary fat in most normal nonadipose tissues but are abnormally elevated in many human cancers and associated with poor prognosis (1). FASN association with poor prognosis may derive in part from FASN function in drug resistance during chemotherapy. Indeed, it has been found that FASN expression and/or activity was increased in drug-selected and -resistant breast (2) and pancreatic (3) cancer cells. It was also found that FASN overexpression causes cellular resistance to DNA-damaging drugs such as doxorubicin and mitoxantrone but not to microtubule modulators such as vinblastine and paclitaxel (4). Decreased ceramide production following doxorubicin treatment via suppression of tumor necrosis factor (TNF)-α production is believed to be one of the mechanisms of FASN-induced resistance to doxorubicin (4).The observation that FASN increases resistance to genotoxic drugs prompted us to hypothesize that FASN overexpression may up-regulate DNA damage response/repair pathways. In this study, we tested this hypothesis with a focus on the repair of DNA double-strand breaks (DSBs), which are commonly induced by the anticancer drugs doxorubicin and mitoxantrone and ionizing radiation. In mammalian cells, DSBs are repaired mainly via homologous recombination (HR) and nonhomologous end-joining (NHEJ) pathways. NHEJ is the predominant form of DSB repair because it occurs during all phases of the cell cycle whereas HR only initiates at late G1 and S phases (5). Hence, we examined NHEJ repair of DSBs and found that FASN up-regulates NHEJ activity and repair of DSBs by increasing poly(ADP-ribose) polymerase 1 (PARP-1) expression via increasing the expression of spec...

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“…LC-MS has frequently been employed in lipidomic analyses, as the introduction of a chromatographic Lipids are multifunctional molecules that serve as the primary components of biological membranes, while also playing important roles in energy storage and signaling (1)(2)(3). Numerous perturbations of lipid metabolism and lipid signaling events have been identifi ed as potentially important factors in the onset and progression of a diverse array of conditions including diabetes ( 4 ), cancer ( 5,6 ), and Alzheimer's disease ( 7 ). Recently, signifi cant disruption of multiple lipid metabolic pathways including sphingolipid metabolism, fatty acid elongation and desaturation, and phospholipid metabolism have been associated with the development of several sight-threatening retinal pathologies methanol has been shown to resolve isobaric mass overlap between plasmalogen lipids and 1-O -alkyl ether-containing lipids ( 34 ).…”

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confidence: 99%

A monophasic extraction strategy for the simultaneous lipidome analysis of polar and nonpolar retina lipids

Lydic

Busik

Reid

2014

Journal of Lipid Research

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Fatty acid synthase plays a role in cancer metabolism beyond providing fatty acids for phospholipid synthesis or sustaining elevations in glycolytic activity

Cited by 78 publications

References 33 publications

To complete its replication cycle, a shrimp virus changes the population of long chain fatty acids during infection via the PI3K-Akt-mTOR-HIF1α pathway

To complete its replication cycle, a shrimp virus changes the population of long chain fatty acids during infection via the PI3K-Akt-mTOR-HIF1α pathway

FASN regulates cellular response to genotoxic treatments by increasing PARP-1 expression and DNA repair activity via NF-κB and SP1

A monophasic extraction strategy for the simultaneous lipidome analysis of polar and nonpolar retina lipids

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