Imperial College London
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ProfessorHectorKeun

Faculty of Medicine, Department of Surgery & Cancer

Professor of Biochemistry
 
 
 
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Contact

 

+44 (0)20 7594 3161h.keun

 
 
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Location

 

officesInstitute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Itkonen:2017:10.18632/oncotarget.16123,
author = {Itkonen, HM and Brown, M and Urbanucci, A and Tredwell, G and Lau, CH and Barfeld, S and Hart, C and Guldvik, IJ and Takhar, M and Heemers, HV and Erho, N and Bloch, K and Davicioni, E and Derua, R and Waelkens, E and Mohler, JL and Clarke, N and Swinnen, JV and Keun, HC and Rekvig, OP and Mills, IG},
doi = {10.18632/oncotarget.16123},
journal = {ONCOTARGET},
pages = {38264--38275},
title = {Lipid degradation promotes prostate cancer cell survival},
url = {http://dx.doi.org/10.18632/oncotarget.16123},
volume = {8},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Itkonen,HM
AU  - Brown,M
AU  - Urbanucci,A
AU  - Tredwell,G
AU  - Lau,CH
AU  - Barfeld,S
AU  - Hart,C
AU  - Guldvik,IJ
AU  - Takhar,M
AU  - Heemers,HV
AU  - Erho,N
AU  - Bloch,K
AU  - Davicioni,E
AU  - Derua,R
AU  - Waelkens,E
AU  - Mohler,JL
AU  - Clarke,N
AU  - Swinnen,JV
AU  - Keun,HC
AU  - Rekvig,OP
AU  - Mills,IG
DO  - 10.18632/oncotarget.16123
EP  - 38275
PY  - 2017///
SN  - 1949-2553
SP  - 38264
TI  - Lipid degradation promotes prostate cancer cell survival
T2  - ONCOTARGET
UR  - http://dx.doi.org/10.18632/oncotarget.16123
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000403311900020&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/50851
VL  - 8
ER  -
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