Imperial College London
Alternate

DrKirillVeselkov

Faculty of Medicine, Department of Surgery & Cancer

Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 3899kirill.veselkov04

 
 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Varshavi:2020:10.1007/s11306-020-01674-2,
author = {Varshavi, D and Varshavi, D and McCarthy, N and Veselkov, K and Keun, HC and Everett, JR},
doi = {10.1007/s11306-020-01674-2},
journal = {Metabolomics},
pages = {1--13},
title = {Metabolic characterization of colorectal cancer cells harbouring different KRAS mutations in codon 12, 13, 61 and 146 using human SW48 isogenic cell lines},
url = {http://dx.doi.org/10.1007/s11306-020-01674-2},
volume = {16},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - IntroductionKirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) mutations occur in approximately one-third of colorectal (CRC) tumours and have been associated with poor prognosis and resistance to some therapeutics. In addition to the well-documented pro-tumorigenic role of mutant Ras alleles, there is some evidence suggesting that not all KRAS mutations are equal and the position and type of amino acid substitutions regulate biochemical activity and transforming capacity of KRAS mutations.ObjectivesTo investigate the metabolic signatures associated with different KRAS mutations in codons 12, 13, 61 and 146 and to determine what metabolic pathways are affected by different KRAS mutations.MethodsWe applied an NMR-based metabonomics approach to compare the metabolic profiles of the intracellular extracts and the extracellular media from isogenic human SW48 CRC cell lines with different KRAS mutations in codons 12 (G12D, G12A, G12C, G12S, G12R, G12V), 13 (G13D), 61 (Q61H) and 146 (A146T) with their wild-type counterpart. We used false discovery rate (FDR)-corrected analysis of variance (ANOVA) to determine metabolites that were statistically significantly different in concentration between the different mutants.ResultsCRC cells carrying distinct KRAS mutations exhibited differential metabolic remodelling, including differences in glycolysis, glutamine utilization and in amino acid, nucleotide and hexosamine metabolism.ConclusionsMetabolic differences among different KRAS mutations might play a role in their different responses to anticancer treatments and hence could be exploited as novel metabolic vulnerabilities to develop more effective therapies against oncogenic KRAS.
AU  - Varshavi,D
AU  - Varshavi,D
AU  - McCarthy,N
AU  - Veselkov,K
AU  - Keun,HC
AU  - Everett,JR
DO  - 10.1007/s11306-020-01674-2
EP  - 13
PY  - 2020///
SN  - 1573-3882
SP  - 1
TI  - Metabolic characterization of colorectal cancer cells harbouring different KRAS mutations in codon 12, 13, 61 and 146 using human SW48 isogenic cell lines
T2  - Metabolomics
UR  - http://dx.doi.org/10.1007/s11306-020-01674-2
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000526305000001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://link.springer.com/article/10.1007%2Fs11306-020-01674-2
UR  - http://hdl.handle.net/10044/1/79989
VL  - 16
ER  -
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