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dc.contributor.authorItkonen, H
dc.contributor.authorBrown, Michael D
dc.contributor.authorUrbanucci, A
dc.contributor.authorTredwell, G
dc.contributor.authorHo Lau, C
dc.contributor.authorBarfeld, S
dc.contributor.authorHart, C
dc.contributor.authorGuldvik, I
dc.contributor.authorTakhar, M
dc.contributor.authorHeemers, H
dc.contributor.authorErho, N
dc.contributor.authorBloch, K
dc.contributor.authorDavicioni, E
dc.contributor.authorDerua, R
dc.contributor.authorWaelkens, E
dc.contributor.authorMohler, J
dc.contributor.authorClarke, Noel W
dc.contributor.authorSwinnen, J
dc.contributor.authorKeun, H
dc.contributor.authorRekvig, O
dc.contributor.authorMills, I
dc.date.accessioned2017-05-12T12:42:07Z
dc.date.available2017-05-12T12:42:07Z
dc.date.issued2017-03-11
dc.identifier.citationLipid degradation promotes prostate cancer cell survival. 2017 Oncotargeten
dc.identifier.issn1949-2553
dc.identifier.pmid28415728
dc.identifier.doi10.18632/oncotarget.16123
dc.identifier.urihttp://hdl.handle.net/10541/620362
dc.description.abstractProstate 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.
dc.language.isoenen
dc.rightsArchived with thanks to Oncotargeten
dc.titleLipid degradation promotes prostate cancer cell survival.en
dc.typeArticleen
dc.contributor.departmentProstate Cancer Research Group, Centre for Molecular Medicine Norway, University of Oslo, Oslo, Norwayen
dc.identifier.journalOncotargeten
refterms.dateFOA2018-12-17T14:55:34Z
html.description.abstractProstate 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.


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