Imperial College London
Alternate

DrPanagiotisVorkas

Faculty of Medicine, Department of Surgery & Cancer

Research Associate
 
 
 
//

Contact

 

p.vorkas

 
 
//

Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Jukes:2021:10.1042/BSR20202915,
author = {Jukes, Z and Freier, A and Glymenaki, M and Brown, R and Parry, L and Want, E and Vorkas, PA and Li, JV},
doi = {10.1042/BSR20202915},
journal = {Bioscience Reports: molecular and cellular biology of the cell surface},
pages = {1--11},
title = {Lipid profiling of mouse intestinal organoids for studying APC mutations},
url = {http://dx.doi.org/10.1042/BSR20202915},
volume = {41},
year = {2021}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Inactivating mutations including both germline and somatic mutations in the adenomatous polyposis coli (APC) gene drives most familial and sporadic colorectal cancers. Understanding the metabolic implications of this mutation will aid to establish its wider impact on cellular behaviour and potentially inform clinical decisions. However, to date, alterations in lipid metabolism induced by APC mutations remain unclear. Intestinal organoids have gained widespread popularity in studying colorectal cancer and chemotherapies, because their 3D structure more accurately mimics an in vivo environment. Here, we aimed to investigate intra-cellular lipid disturbances induced by APC gene mutations in intestinal organoids using a reversed-phase ultra-high-performance liquid chromatography mass spectrometry (RP-UHPLC-MS)-based lipid profiling method. Lipids of the organoids grown from either wild-type (WT) or mice with APC mutations (Lgr5–EGFP-IRES-CreERT2Apcfl/fl) were extracted and analysed using RP-UHPLC-MS. Levels of phospholipids (e.g. PC(16:0/16:0), PC(18:1/20:0), PC(38:0), PC(18:1/22:1)), ceramides (e.g. Cer(d18:0/22:0), Cer(d42:0), Cer(d18:1/24:1)) and hexosylceramides (e.g. HexCer(d18:1/16:0), HexCer(d18:1/22:0)) were higher in Apcfl/fl organoids, whereas levels of sphingomyelins (e.g. SM(d18:1/14:0), SM(d18:1/16:0)) were lower compared with WT. These observations indicate that cellular metabolism of sphingomyelin was up-regulated, resulting in the cellular accumulation of ceramides and production of HexCer due to the absence of Apcfl/fl in the organoids. Our observations demonstrated lipid profiling of organoids and provided an enhanced insight into the effects of the APC mutations on lipid metabolism, making for a valuable addition to screening options of the organoid lipidome.
AU  - Jukes,Z
AU  - Freier,A
AU  - Glymenaki,M
AU  - Brown,R
AU  - Parry,L
AU  - Want,E
AU  - Vorkas,PA
AU  - Li,JV
DO  - 10.1042/BSR20202915
EP  - 11
PY  - 2021///
SN  - 0144-8463
SP  - 1
TI  - Lipid profiling of mouse intestinal organoids for studying APC mutations
T2  - Bioscience Reports: molecular and cellular biology of the cell surface
UR  - http://dx.doi.org/10.1042/BSR20202915
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000634682900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://portlandpress.com/bioscirep/article/41/3/BSR20202915/227920/Lipid-profiling-of-mouse-intestinal-organoids-for
UR  - http://hdl.handle.net/10044/1/88264
VL  - 41
ER  -
Download