Fatty Acid Synthase Activity as a Target for c-Met Driven Prostate Cancer

2013 ◽  
Author(s):  
David T. Coleman
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Fatty Acid Synthase

scholarly journals Fatty Acid Synthase Polymorphisms, Tumor Expression, Body Mass Index, Prostate Cancer Risk, and Survival

2010 ◽  
Vol 28 (25) ◽  
pp. 3958-3964 ◽  
Author(s):  
Paul L. Nguyen ◽  
Jing Ma ◽  
Jorge E. Chavarro ◽  
Matthew L. Freedman ◽  
Rosina Lis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Body Mass Index ◽  
Fatty Acid ◽  
Body Mass ◽  
Fatty Acid Synthase ◽  
Prostate Cancer Risk ◽  
De Novo Lipogenesis ◽  
Variant Allele ◽  
Specific Mortality ◽  
Tumor Expression

Purpose Fatty acid synthase (FASN) regulates de novo lipogenesis, body weight, and tumor growth. We examined whether common germline single nucleotide polymorphisms (SNPs) in the FASN gene affect prostate cancer (PCa) risk or PCa-specific mortality and whether these effects vary by body mass index (BMI). Methods In a prospective nested case-control study of 1,331 white patients with PCa and 1,267 age-matched controls, we examined associations of five common SNPs within FASN (and 5 kb upstream/downstream, R2 > 0.8) with PCa incidence and, among patients, PCa-specific death and tested for an interaction with BMI. Survival analyses were repeated for tumor FASN expression (n = 909). Results Four of the five SNPs were associated with lethal PCa. SNP rs1127678 was significantly related to higher BMI and interacted with BMI for both PCa risk (Pinteraction = .004) and PCa mortality (Pinteraction = .056). Among overweight men (BMI ≥ 25 kg/m2), but not leaner men, the homozygous variant allele carried a relative risk of advanced PCa of 2.49 (95% CI, 1.00 to 6.23) compared with lean men with the wild type. Overweight patients carrying the variant allele had a 2.04 (95% CI, 1.31 to 3.17) times higher risk of PCa mortality. Similarly, overweight patients with elevated tumor FASN expression had a 2.73 (95% CI, 1.05 to 7.08) times higher risk of lethal PCa (Pinteraction = .02). Conclusion FASN germline polymorphisms were significantly associated with risk of lethal PCa. Significant interactions of BMI with FASN polymorphisms and FASN tumor expression suggest FASN as a potential link between obesity and poor PCa outcome and raise the possibility that FASN inhibition could reduce PCa-specific mortality, particularly in overweight men.

Inhibition of fatty acid synthase activity in prostate cancer cells by dutasteride

The Prostate ◽  
2007 ◽  
Vol 67 (10) ◽  
pp. 1111-1120 ◽  
Author(s):  
Lucy J. Schmidt ◽  
Karla V. Ballman ◽  
Donald J. Tindall
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthase ◽  
Prostate Cancer Cells

High-level expression of fatty acid synthase in human prostate cancer tissues is linked to activation and nuclear localization of Akt/PKB

2005 ◽  
Vol 206 (2) ◽  
pp. 214-219 ◽  
Author(s):  
Tine Van de Sande ◽  
Tania Roskams ◽  
Evelyne Lerut ◽  
Steven Joniau ◽  
Hein Van Poppel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Nuclear Localization ◽  
Fatty Acid Synthase ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
High Level Expression ◽  
High Level ◽  
Cancer Tissues

scholarly journals Emerging Therapeutic Activity of Davallia formosana on Prostate Cancer Cells through Coordinated Blockade of Lipogenesis and Androgen Receptor Expression

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 914
Author(s):  
Po-Fan Hsieh ◽  
Wen-Ping Jiang ◽  
Shih-Yin Huang ◽  
Praveenkumar Basavaraj ◽  
Jin-Bin Wu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Androgen Receptor ◽  
Molecular Basis ◽  
Fatty Acid Synthase ◽  
Specific Antigen ◽  
Receptor Expression ◽  
Migration And Invasion ◽  
Therapeutic Activity ◽  
Castration Resistant

Background: Prostate cancer (PCa) is the most prevalent malignancy diagnosed in men in Western countries. There is currently no effective therapy for advanced PCa aggressiveness, including castration-resistant progression. The aim of this study is to evaluate the potential efficacy and determine the molecular basis of Davallia formosana (DF) in PCa. Methods: LNCaP (androgen-sensitive) and C4-2 (androgen-insensitive/castration-resistant) PCa cells were utilized in this study. An MTT-based method, a wound healing assay, and the transwell method were performed to evaluate cell proliferation, migration, and invasion. Intracellular fatty acid levels and lipid droplet accumulation were analyzed to determine lipogenesis. Moreover, apoptotic assays and in vivo experiments were conducted. Results: DF ethanol extract (DFE) suppressed proliferation, migration, and invasion in PCa cells. DFE attenuated lipogenesis through inhibition of the expression of sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FASN). Moreover, DFE decreased androgen receptor (AR) and prostate-specific antigen (PSA) expression in PCa cells. We further showed the potent therapeutic activity of DFE by repressing the growth and leading to apoptosis of subcutaneous C4-2 tumors in a xenograft mouse model. Conclusions: These data provide a new molecular basis of DFE in PCa cells, and co-targeting SREBP-1/FASN/lipogenesis and the AR axis by DFE could be employed as a novel and promising strategy for the treatment of PCa.

scholarly journals FABP5 coordinates lipid signaling that promotes prostate cancer metastasis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Gregory Carbonetti ◽  
Tessa Wilpshaar ◽  
Jessie Kroonen ◽  
Keith Studholme ◽  
Cynthia Converso ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Nuclear Receptor ◽  
Fatty Acid Synthase ◽  
Cancer Metastasis ◽  
Receptor Activation ◽  
Lipid Signaling ◽  
Fatty Acid Binding

AbstractProstate cancer (PCa) is defined by dysregulated lipid signaling and is characterized by upregulation of lipid metabolism-related genes including fatty acid binding protein 5 (FABP5), fatty acid synthase (FASN), and monoacylglycerol lipase (MAGL). FASN and MAGL are enzymes that generate cellular fatty acid pools while FABP5 is an intracellular chaperone that delivers fatty acids to nuclear receptors to enhance PCa metastasis. Since FABP5, FASN, and MAGL have been independently implicated in PCa progression, we hypothesized that FABP5 represents a central mechanism linking cytosolic lipid metabolism to pro-metastatic nuclear receptor signaling. Here, we show that the abilities of FASN and MAGL to promote nuclear receptor activation and PCa metastasis are critically dependent upon co-expression of FABP5 in vitro and in vivo. Our findings position FABP5 as a key driver of lipid-mediated metastasis and suggest that disruption of lipid signaling via FABP5 inhibition may constitute a new avenue to treat metastatic PCa.

scholarly journals RNA-seq reveals novel mechanistic targets of withaferin A in prostate cancer cells

2020 ◽  
Vol 41 (6) ◽  
pp. 778-789 ◽  
Author(s):  
Su-Hyeong Kim ◽  
Eun-Ryeong Hahm ◽  
Krishna B Singh ◽  
Sruti Shiva ◽  
Jacob Stewart-Ornstein ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Acid Synthesis ◽  
Acetyl Coa Carboxylase ◽  
Rna Seq ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Citrate Lyase

Abstract Withaferin A (WA) is a promising phytochemical exhibiting in vitro and in vivo anticancer activities against prostate and other cancers, but the mechanism of its action is not fully understood. In this study, we performed RNA-seq analysis using 22Rv1 human prostate cancer cell line to identify mechanistic targets of WA. Kyoto Encyclopedia of Genes and Genomes pathway analysis of the differentially expressed genes showed most significant enrichment of genes associated with metabolism. These results were validated using LNCaP and 22Rv1 human prostate cancer cells and Hi-Myc transgenic mice as models. The intracellular levels of acetyl-CoA, total free fatty acids and neutral lipids were decreased significantly following WA treatment in both cells, which was accompanied by downregulation of mRNA (confirmed by quantitative reverse transcription-polymerase chain reaction) and protein levels of key fatty acid synthesis enzymes, including ATP citrate lyase, acetyl-CoA carboxylase 1, fatty acid synthase and carnitine palmitoyltransferase 1A. Ectopic expression of c-Myc, but not constitutively active Akt, conferred a marked protection against WA-mediated suppression of acetyl-CoA carboxylase 1 and fatty acid synthase protein expression, and clonogenic cell survival. WA was a superior inhibitor of cell proliferation and fatty acid synthesis in comparison with known modulators of fatty acid metabolism including cerulenin and etomoxir. Intraperitoneal WA administration to Hi-Myc transgenic mice (0.1 mg/mouse, three times/week for 5 weeks) also resulted in a significant decrease in circulating levels of total free fatty acids and phospholipids, and expression of ATP citrate lyase, acetyl-CoA carboxylase 1, fatty acid synthase and carnitine palmitoyltransferase 1A proteins in the prostate in vivo.

Speckle‐type POZ protein suppresses lipid accumulation and prostate cancer growth by stabilizing fatty acid synthase

The Prostate ◽  
2019 ◽  
Vol 79 (8) ◽  
pp. 864-871 ◽  
Author(s):  
Xiaokun Gang ◽  
Lili Xuan ◽  
Xue Zhao ◽  
You Lv ◽  
Fei Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Lipid Accumulation ◽  
Fatty Acid Synthase ◽  
Cancer Growth
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