Cholesteryl Esters: Fueling the Fury of Prostate Cancer

Peck, Barrie; Schulze, Almut

doi:10.1016/j.cmet.2014.02.012

Cited by 21 publications

(23 citation statements)

References 10 publications

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“…Metabolic reprogramming is one of the hallmarks in cancer progression, and high level of CE has been reported in several cancers including breast cancer, prostate cancer, pancreatic cancer, leukemia, glioma . Accumulation of CE via ACAT‐1 provides a mechanism to keep high metabolic activity and avoid toxicity from excess free cholesterol .…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, up regulation of SREBP‐1 is considered as an evident in the metastasis in breast cancer cell . The activity of SREBPs is tightly regulated by a negative feedback loop triggered by ER membrane cholesterol . SREBPs also play an important role in LDLR regulation in human breast cancer cell.…”

Section: Discussionmentioning

confidence: 99%

“…It catalyzes the formation of cholesteryl esters from long‐chain fatty acyl coenzyme A and cholesterol. Increased ACAT‐1 expression and CE level have been reported in various human cancers including breast cancer . Thus, targeting the lipid metabolism in TNBC may be a new and exciting therapeutic approach.…”

Section: Introductionmentioning

confidence: 99%

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Disrupting cholesterol esterification by bitter melon suppresses triple‐negative breast cancer cell growth

Shim

Sur²,

Steele³

et al. 2018

Molecular Carcinogenesis

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Triple negative breast cancer (TNBC) is aggressive with a worse prognosis. We have recently shown that bitter melon extract (BME) treatment was more effective in inhibition of TNBC tumor growth in mouse models as compared to ER positive breast tumor growth. Aberrant dysregulation of lipid metabolism is associated with breast cancer progression, however, anti-cancer mechanism of BME linking lipid metabolism in breast cancer growth remains unexplored. Here, we observed that accumulation of esterified cholesterol was reduced in BME treated TNBC cell lines as compared to control cells. We next evaluated expression levels of acyl-CoA: cholesterol acyltransferase 1 (ACAT-1) in TNBC cells treated with BME. Our results demonstrated that BME treatment inhibited ACAT-1 expression in TNBC cells. Subsequently, we found that sterol regulatory element-binding proteins-1 and -2, and FASN was significantly reduced in BME treated TNBC cell lines. Low-density lipoprotein receptor was also downregulated in BME treated TNBC cells as compared to control cells. We further demonstrated that BME feeding reduced tumor growth in TNBC mammospheres implanted into NSG mice, and inhibits ACAT-1 expression. To our knowledge, this is the first report demonstrating BME suppresses TNBC cell growth through ACAT-1 inhibition, and have potential for additional therapeutic regimen against human breast cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Disrupting cholesterol esterification by bitter melon suppresses triple‐negative breast cancer cell growth

Shim

Sur²,

Steele³

et al. 2018

Molecular Carcinogenesis

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“…Elevated expression of ELOVL7 , a human homolog of sit , is associated with steroidogenic tissues and prostate cancer progression (Tamura et al, 2009), yet the molecular basis for this relationship remains unclear. Prostate cancer cells acquire the ability to enhance cholesterol uptake, potentially making the cancers more aggressive, but the underlying molecular basis is poorly understood (Peck and Schulze, 2014; Yue et al, 2014). Our data suggest that Sit may play a role in this process.…”

Section: Discussionmentioning

confidence: 99%

A Drosophila Genome-Wide Screen Identifies Regulators of Steroid Hormone Production and Developmental Timing

et al. 2016

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Summary Steroid hormones control important developmental processes and are linked to many diseases. To systematically identify genes and pathways required for steroid production, we performed a Drosophila genome-wide in vivo RNAi screen and identified 1,906 genes with potential roles in steroidogenesis and developmental timing. Here, we use our screen as a resource to identify mechanisms regulating intracellular levels of cholesterol, a substrate for steroidogenesis. We identify a conserved fatty acid elongase that underlies a mechanism which adjusts cholesterol trafficking and steroidogenesis with nutrition and developmental programs. Additionally, we demonstrate the existence of an autophagosomal cholesterol mobilization mechanism and show that activation of this system rescues Niemann Pick type C1-deficiency that causes a disorder characterized by cholesterol accumulation. These cholesterol trafficking mechanisms are regulated by TOR and feedback signaling that couples steroidogenesis with growth and ensure proper maturation timing. These results reveal genes regulating steroidogenesis during development that likely modulate disease mechanisms.

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“…Recent studies show that LCAT also serves in reverse cholesterol transport and polyunsaturated CE synthesis, whereas, ACAT2[8] (one isoform of ACAT) promotes accumulation of monounsaturated and saturated CE in lipoprotein particles containing apolipoprotein B[9]. Given the importance of cholesterol homeostasis for normal functions of cells, abnormal CE levels are often linked with various pathological conditions including metabolic disorders[10], heart disease[11], and cancer [12, 13]. CE profiling, a subset study of metabolomics and lipidomics, has been frequently used as a means to discover biomarkers for disease monitoring or diagnosis[14].…”

Section: Introductionmentioning

confidence: 99%

Uncovering Structural Diversity of Unsaturated Fatty Acyls in Cholesteryl Esters via Photochemical Reaction and Tandem Mass Spectrometry

Ren

Franklin

Xia

2017

J. Am. Soc. Mass Spectrom.

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Mass spectrometry analysis of cholesteryl esters (CEs) faces several challenges with one of them being the determination of the carbon-carbon double bond (C=C) locations within unsaturated fatty acyl chains. Paternò-Büchi (PB) reaction, a photochemical reaction based on the addition of acetone to C=C, is capable of C=C location determination when coupled with tandem mass spectrometry (MS/MS). In this study, the PB reaction conditions were tailored for CEs and subsequent nanoelectrospray ionization (nanoESI). A solvent system containing acetone/methanol/dichloromethane/water (40/30/20/10, volume ratios) and 100 μM LiOH was determined to be optimal, resulting in reasonable PB reaction yield (~30%) and good ionization efficiency (forming lithium adduct of CEs). Collision-induced dissociation (CID) of the PB reaction products produced characteristic fragment ions of CE together with those modified by the PB reactions, such as lithiated fatty acyl ([FA+Li]+) and its PB product ([FA-PB+Li]+). MS3 CID of [FA-PB +Li]+ led to abundant C=C diagnostic ion formation, which was used for C=C location determination and isomer quantitation. A PB-MS3 CID approach was developed and applied for CE analysis from human plasma. A series of unsaturated CEs was identified with specific C=C locations within fatty acyl chains. Absolute quantitation for each CE species was achieved including co-existing C=C location isomers, such as Δ9 and Δ11 isomers of CE 18:1 and ω-6 and ω-3 isomers of CE 18:3. These results show that PB-MS/MS is useful in uncovering structural diversity of CEs due to unsaturation in fatty acyls, which is often undetected from current lipid analysis approach.

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Cholesteryl Esters: Fueling the Fury of Prostate Cancer

Cited by 21 publications

References 10 publications

Disrupting cholesterol esterification by bitter melon suppresses triple‐negative breast cancer cell growth

Disrupting cholesterol esterification by bitter melon suppresses triple‐negative breast cancer cell growth

A Drosophila Genome-Wide Screen Identifies Regulators of Steroid Hormone Production and Developmental Timing

Uncovering Structural Diversity of Unsaturated Fatty Acyls in Cholesteryl Esters via Photochemical Reaction and Tandem Mass Spectrometry

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