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| Status |
Public on Mar 03, 2017 |
| Title |
Lipid degradation promotes prostate cancer cell survival |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Two biological replicates for prostate cancer cell line (LNCaP) and cell line representing normal prostate epithelium (RWPE-1), transfected with scrambled siRNA or two different siRNAs targeting ECI2. RNA was extracted and used for RNA-sequencing.
The processed files provided are compressed folders containing multiple output files from CuffDiff runs estimating differentially expressed transcripts between the indicated ECI2 siRNA treated cells versus cells treated with Scrambled siRNAs.
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| Contributor(s) |
Itkonen HM, Brown M, Urbanucci A, Tredwell G, Lau CH, Barfeld S, Guldvik IJ, Bloch K, Takhar M, Heemers H, Erho N, Davicioni E, Waelkens E, Derua R, Swinnen JV, Keun H, Rekvig O, Hart C, Heemers HV, Mohler JL, Clarke N, Mills IG |
| Citation(s) |
28415728 |
| Submission date |
Nov 16, 2015 |
| Last update date |
Oct 04, 2022 |
| Contact name |
Alfonso Urbanucci |
| E-mail(s) |
alfonsou@ifi.uio.no
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| Phone |
45048687
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| Organization name |
Oslo University Hospital
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| Street address |
Trondheimsveien 8
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| City |
Oslo |
| State/province |
Oslo |
| ZIP/Postal code |
0560 |
| Country |
Norway |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA302270 |
| SRA |
SRP066238 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE75035_04_cuffdiff_LNCaP_ECI1_vs_Scr.tar.gz |
22.8 Mb |
(ftp)(http) |
TAR |
| GSE75035_04_cuffdiff_LNCaP_ECI2_vs_Scr.tar.gz |
23.0 Mb |
(ftp)(http) |
TAR |
| GSE75035_04_cuffdiff_RWPE_ECI1_vs_Scr.tar.gz |
20.1 Mb |
(ftp)(http) |
TAR |
| GSE75035_04_cuffdiff_RWPE_ECI2_vs_Scr.tar.gz |
20.2 Mb |
(ftp)(http) |
TAR |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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