Imperial College London
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Dr Olivier E. Pardo

Faculty of Medicine, Department of Surgery & Cancer

Reader in Cancer Cell Signalling
 
 
 
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Contact

 

+44 (0)20 7594 2814o.pardo Website CV

 
 
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Location

 

145ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Poursaitidis:2017:10.1016/j.celrep.2017.02.054,
author = {Poursaitidis, I and Wang, X and Crighton, T and Labuschagne, C and Mason, D and Cramer, SL and Triplett, K and Roy, R and Pardo, OE and Seckl, MJ and Rowlinson, SW and Stone, E and Lamb, RF},
doi = {10.1016/j.celrep.2017.02.054},
journal = {CELL REPORTS},
pages = {2547--2556},
title = {Oncogene-Selective Sensitivity to Synchronous Cell Death following Modulation of the Amino Acid Nutrient Cystine},
url = {http://dx.doi.org/10.1016/j.celrep.2017.02.054},
volume = {18},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Cancer cells reprogram their metabolism, altering both uptake and utilization of extracellular nutrients. We individually depleted amino acid nutrients from isogenic cells expressing commonly activated oncogenes to identify correspondences between nutrient supply and viability. In HME (human mammary epithelial) cells, deprivation of cystine led to increased cell death in cells expressing an activated epidermal growth factor receptor (EGFR) mutant. Cell death occurred via synchronous ferroptosis, with generation of reactive oxygen species (ROS). Hydrogen peroxide promoted cell death, as both catalase and inhibition of NADPH oxidase 4 (NOX4) blocked ferroptosis. Blockade of EGFR or mitogen-activated protein kinase (MAPK) signaling similarly protected cells from ferroptosis, whereas treatment of xenografts derived from EGFR mutant non-small-cell lung cancer (NSCLC) with a cystine-depleting enzyme inhibited tumor growth in mice. Collectively, our results identify a potentially exploitable sensitization of some EGFR/MAPK-driven tumors to ferroptosis following cystine depletion.
AU  - Poursaitidis,I
AU  - Wang,X
AU  - Crighton,T
AU  - Labuschagne,C
AU  - Mason,D
AU  - Cramer,SL
AU  - Triplett,K
AU  - Roy,R
AU  - Pardo,OE
AU  - Seckl,MJ
AU  - Rowlinson,SW
AU  - Stone,E
AU  - Lamb,RF
DO  - 10.1016/j.celrep.2017.02.054
EP  - 2556
PY  - 2017///
SN  - 2211-1247
SP  - 2547
TI  - Oncogene-Selective Sensitivity to Synchronous Cell Death following Modulation of the Amino Acid Nutrient Cystine
T2  - CELL REPORTS
UR  - http://dx.doi.org/10.1016/j.celrep.2017.02.054
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000397330000001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/45992
VL  - 18
ER  -
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