Imperial College London
Alternate

Emeritus ProfessorJeremyNicholson

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Emeritus Professor of Biological Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 3195j.nicholson Website

 
 
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Assistant

 

Ms Wendy Torto +44 (0)20 7594 3225

 
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Location

 

Office no. 665Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Koundouros:2020:10.1016/j.cell.2020.05.053,
author = {Koundouros, N and Karali, E and Tripp, A and Valle, A and Inglese, P and Perry, NJS and Magee, DJ and Virmouni, SA and Elder, GA and Tyson, AL and Doria, ML and van, Weverwijk A and Soares, RF and Isacke, CM and Nicholson, JK and Glen, RC and Takats, Z and Poulogiannis, G},
doi = {10.1016/j.cell.2020.05.053},
journal = {Cell},
pages = {1596--1611.e27},
title = {Metabolic fingerprinting links oncogenic PIK3CA with enhanced arachidonic acid-derived eicosanoids},
url = {http://dx.doi.org/10.1016/j.cell.2020.05.053},
volume = {181},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Oncogenic transformation is associated with profound changes in cellular metabolism, but whether tracking these can improve disease stratification or influence therapy decision-making is largely unknown. Using the iKnife to sample the aerosol of cauterized specimens, we demonstrate a new mode of real-time diagnosis, coupling metabolic phenotype to mutant PIK3CA genotype. Oncogenic PIK3CA results in an increase in arachidonic acid and a concomitant overproduction of eicosanoids, acting to promote cell proliferation beyond a cell-autonomous manner. Mechanistically, mutant PIK3CA drives a multimodal signaling network involving mTORC2-PKCζ-mediated activation of the calcium-dependent phospholipase A2 (cPLA2). Notably, inhibiting cPLA2 synergizes with fatty acid-free diet to restore immunogenicity and selectively reduce mutant PIK3CA-induced tumorigenicity. Besides highlighting the potential for metabolic phenotyping in stratified medicine, this study reveals an important role for activated PI3K signaling in regulating arachidonic acid metabolism, uncovering a targetable metabolic vulnerability that largely depends on dietary fat restriction.
AU  - Koundouros,N
AU  - Karali,E
AU  - Tripp,A
AU  - Valle,A
AU  - Inglese,P
AU  - Perry,NJS
AU  - Magee,DJ
AU  - Virmouni,SA
AU  - Elder,GA
AU  - Tyson,AL
AU  - Doria,ML
AU  - van,Weverwijk A
AU  - Soares,RF
AU  - Isacke,CM
AU  - Nicholson,JK
AU  - Glen,RC
AU  - Takats,Z
AU  - Poulogiannis,G
DO  - 10.1016/j.cell.2020.05.053
EP  - 1611
PY  - 2020///
SN  - 0092-8674
SP  - 1596
TI  - Metabolic fingerprinting links oncogenic PIK3CA with enhanced arachidonic acid-derived eicosanoids
T2  - Cell
UR  - http://dx.doi.org/10.1016/j.cell.2020.05.053
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000543822100016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.sciencedirect.com/science/article/pii/S0092867420306863?via%3Dihub
UR  - http://hdl.handle.net/10044/1/81944
VL  - 181
ER  -
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