Stearoyl CoA Desaturase (SCD) Facilitates Proliferation of Prostate Cancer Cells through Enhancement of Androgen Receptor Transactivation

Kim, Seung-Jin; Choi, Hojung; Park, Sung Soo; Chang, Chawnshang; Kim, Eungseok

doi:10.1007/s10059-011-0043-5

Cited by 52 publications

(43 citation statements)

References 33 publications

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“…Many studies support the idea that cancer cells activate the cell intrinsic biosynthesis pathway for fatty acid metabolism to produce de novo lipogenesis (87, 88). Scd1 and Soat1 have been previously implicated in proliferation of other cancers including lung, prostate, and kidney (41, 55, 89) as well as glioblastoma and breast cancer (52, 56), respectively. Scd1 has been shown to decrease the ratio of saturated to unsaturated fatty acids during G1 phase of cell cycle, and to be essential for cancer cell growth and survival (88).…”

Section: Discussionmentioning

confidence: 99%

Runx1 Role in Epithelial and Cancer Cell Proliferation Implicates Lipid Metabolism and Scd1 and Soat1 Activity

et al. 2018

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The role of lipid metabolism in epithelial stem cell (SC) function and carcinogenesis is poorly understood. The transcription factor Runx1 is known to regulate proliferation in mouse epithelial hair follicle (HF) SCs in vivo and in several mouse and human epithelial cancers. We found a novel subset of in vivo Runx1 HFSC target genes related to lipid metabolism and demonstrated changes in distinct classes of lipids driven by Runx1. Inhibition of lipid-enzymes Scd1 and Soat1 activity synergistically reduces proliferation of mouse skin epithelial cells and of human skin and oral squamous cell carcinoma cultured lines. Varying Runx1 levels induces changes in skin monounsaturated fatty acids (e.g., oleate, a product of Scd1) as shown by our lipidome analysis. Furthermore, varying Runx1 levels, the inhibition of Scd1, or the addition of Scd1-product oleate, individually affects the plasma membrane organization (or fluidity) in mouse keratinocytes. These factors also affect the strength of signal transduction through the membranes for Wnt, a pathway that promotes epithelial (cancer) cell proliferation and HFSC activation. Our working model is that HFSC factor Runx1 modulates the fatty acid production, which affects membrane organization, facilitating signal transduction for rapid proliferation of normal and cancer epithelial cells. Stem Cells 2018;36:1603-1616.

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Section: Discussionmentioning

confidence: 99%

Runx1 Role in Epithelial and Cancer Cell Proliferation Implicates Lipid Metabolism and Scd1 and Soat1 Activity

et al. 2018

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“…Whether AR8 activates SREBP-1 is unknown. Interestingly, inhibition of SREBP-1, ACACA, FASN, or SCD-1 results in decreased AR expression and activity [19, 78, 79]. Concomitant overexpression of AR and FASN in prostate is sufficient to induce adenocarcinoma in mice [17].…”

Section: De Novo Lipogenesis In Prostate Cancermentioning

confidence: 99%

“…While the effects of dietary MUFA remain quite a mystery, two studies have highlighted a role for SCD-1, the enzyme responsible for de novo MUFA synthesis, in the promotion of prostate cancer [26, 78]. While these studies describe the role of MUFA in the de novo lipogenesis pathway of cancer, no study has investigated the interplay between dietary fat and SCD-1 in prostate cancer.…”

Section: Dietary Lipids and Prostate Cancermentioning

confidence: 99%

Lipids and prostate cancer

Suburu

Chen

2012

Prostaglandins & Other Lipid Mediators

112

100

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The role of lipid metabolism has gained particular interest in prostate cancer research. A large body of literature has outlined the unique upregulation of de novo lipid synthesis in prostate cancer. Concordant with this lipogenic phenotype is a metabolic shift, in which cancer cells use alternative enzymes and pathways to facilitate the production of fatty acids. These newly synthesized lipids may support a number of cellular processes to promote cancer cell proliferation and survival. Hence, de novo lipogenesis is under intense investigation as a therapeutic target. Epidemiologic studies suggest dietary fat may also contribute to prostate cancer; however, whether dietary lipids and de novo synthesized lipids are differentially metabolized remains unclear. Here, we highlight the lipogenic nature of prostate cancer, especially the promotion of de novo lipid synthesis, and the significance of various dietary lipids in prostate cancer development and progression.

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“…SCD, the rate‐limiting enzyme in the biosynthesis of monounsaturated fatty acids, is highly expressed in prostate cancer. SCD can promote proliferation of androgen receptor (AR)‐positive LNCaP prostate cancer cells and enhance dihydrotestosterone (DHT)‐induced AR transcriptional activity, resulting in increased expression of prostate‐specific antigen (PSA) and kallikrein‐related peptidase 2 (KLK2) [59, 60].…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic alterations in human prostate cancer cell LNCaP tumor xenograft modulated by dietary phenethyl isothiocyanate

Wang

2012

Molecular Carcinogenesis

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Temporal growth of tumor xenografts in mice on a control diet was compared to mice supplemented daily with 3 µmol/g of the cancer preventive compound phenethyl isothiocyanate. Phenethyl isothiocyanate decreased the rate of tumor growth. The effects of phenethyl isothiocyanate on tumor growth were examined by RNAseq to elucidate molecular changes that may contribute to tumor growth suppression. Bio-informatic analysis of differentially expressed genes identified changes in inflammation and extracellular matrix pathways that were modulated by treatment with phenethyl isothiocyanate. Specific gene expression changes in these pathways included up-regulation of insulin-like growth factor binding protein 3, fibronectin, thyroxine degradation enzyme, and down regulation of integrin beta 6. In addition, feeding phenethyl isothiocyanate induced alternative splicing of gene variants. This study represents the first use of RNAseq to analyze tumors from animals consuming dietary phenethyl isothiocyanate and to identify potential molecular signatures that may explain the cancer protective effect of this compound.

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Stearoyl CoA Desaturase (SCD) Facilitates Proliferation of Prostate Cancer Cells through Enhancement of Androgen Receptor Transactivation

Cited by 52 publications

References 33 publications

Runx1 Role in Epithelial and Cancer Cell Proliferation Implicates Lipid Metabolism and Scd1 and Soat1 Activity

Runx1 Role in Epithelial and Cancer Cell Proliferation Implicates Lipid Metabolism and Scd1 and Soat1 Activity

Lipids and prostate cancer

Transcriptomic alterations in human prostate cancer cell LNCaP tumor xenograft modulated by dietary phenethyl isothiocyanate

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