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    Lipid degradation promotes prostate cancer cell survival.

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    Authors
    Itkonen, H
    Brown, Michael D
    Urbanucci, A
    Tredwell, G
    Ho Lau, C
    Barfeld, S
    Hart, C
    Guldvik, I
    Takhar, M
    Heemers, H
    Erho, N
    Bloch, K
    Davicioni, E
    Derua, R
    Waelkens, E
    Mohler, J
    Clarke, Noel W
    Swinnen, J
    Keun, H
    Rekvig, O
    Mills, I
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    Affiliation
    Prostate Cancer Research Group, Centre for Molecular Medicine Norway, University of Oslo, Oslo, Norway
    Issue Date
    2017-03-11
    
    Metadata
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    Abstract
    Prostate cancer is the most common male cancer and androgen receptor (AR) is the major driver of the disease. Here we show that Enoyl-CoA delta isomerase 2 (ECI2) is a novel AR-target that promotes prostate cancer cell survival. Increased ECI2 expression predicts mortality in prostate cancer patients (p = 0.0086). ECI2 encodes for an enzyme involved in lipid metabolism, and we use multiple metabolite profiling platforms and RNA-seq to show that inhibition of ECI2 expression leads to decreased glucose utilization, accumulation of fatty acids and down-regulation of cell cycle related genes. In normal cells, decrease in fatty acid degradation is compensated by increased consumption of glucose, and here we demonstrate that prostate cancer cells are not able to respond to decreased fatty acid degradation. Instead, prostate cancer cells activate incomplete autophagy, which is followed by activation of the cell death response. Finally, we identified a clinically approved compound, perhexiline, which inhibits fatty acid degradation, and replicates the major findings for ECI2 knockdown. This work shows that prostate cancer cells require lipid degradation for survival and identifies a small molecule inhibitor with therapeutic potential.
    Citation
    Lipid degradation promotes prostate cancer cell survival. 2017 Oncotarget
    Journal
    Oncotarget
    URI
    http://hdl.handle.net/10541/620362
    DOI
    10.18632/oncotarget.16123
    PubMed ID
    28415728
    Type
    Article
    Language
    en
    ISSN
    1949-2553
    ae974a485f413a2113503eed53cd6c53
    10.18632/oncotarget.16123
    Scopus Count
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