Imperial College London
Alternate

DrJimEllis

Faculty of Medicine, Department of Surgery & Cancer

Stable Isotope Labelling (SIL) Spec & Senior Anal Scientist
 
 
 
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Contact

 

jim.ellis Website

 
 
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Location

 

7NCommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Trousil:2014:10.1158/0008-5472.CAN-13-2409,
author = {Trousil, S and Lee, P and Pinato, DJ and Ellis, JK and Dina, R and Aboagye, EO and Keun, HC and Sharma, R},
doi = {10.1158/0008-5472.CAN-13-2409},
journal = {Cancer Research},
pages = {6867--6877},
title = {Alterations of choline phospholipid metabolism in endometrial cancer are caused by choline kinase alpha overexpression and a hyperactivated deacylation pathway},
url = {http://dx.doi.org/10.1158/0008-5472.CAN-13-2409},
volume = {74},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Metabolic rearrangements subsequent to malignant transformation are not well characterized in endometrial cancer. Identification of altered metabolites could facilitate imaging-guided diagnosis, treatment surveillance, and help to identify new therapeutic options. Here, we used high-resolution magic angle spinning magnetic resonance mass spectroscopy on endometrial cancer surgical specimens and normal endometrial tissue to investigate the key modulators that might explain metabolic changes, incorporating additional investigations using qRT-PCR, Western blotting, tissue microarrays (TMA), and uptake assays of [3H]-labeled choline. Lipid metabolism was severely dysregulated in endometrial cancer with various amino acids, inositols, nucleobases, and glutathione also altered. Among the most important lipid-related alterations were increased phosphocholine levels (increased 70% in endometrial cancer). Mechanistic investigations revealed that changes were not due to altered choline transporter expression, but rather due to increased expression of choline kinase α (CHKA) and an activated deacylation pathway, as indicated by upregulated expression of the catabolic enzymes LYPLA1, LYPLA2, and GPCPD1. We confirmed the significance of CHKA overexpression on a TMA, including a large series of endometrial hyperplasia, atypical hyperplasia, and adenocarcinoma tissues, supporting a role for CHKA in malignant transformation. Finally, we documented several-fold increases in the uptake of [3H]choline in endometrial cancer cell lines compared with normal endometrial stromal cells. Our results validate deregulated choline biochemistry as an important source of noninvasive imaging biomarkers for endometrial cancer. Cancer Res; 74(23); 6867–77. ©2014 AACR.
AU  - Trousil,S
AU  - Lee,P
AU  - Pinato,DJ
AU  - Ellis,JK
AU  - Dina,R
AU  - Aboagye,EO
AU  - Keun,HC
AU  - Sharma,R
DO  - 10.1158/0008-5472.CAN-13-2409
EP  - 6877
PY  - 2014///
SN  - 0008-5472
SP  - 6867
TI  - Alterations of choline phospholipid metabolism in endometrial cancer are caused by choline kinase alpha overexpression and a hyperactivated deacylation pathway
T2  - Cancer Research
UR  - http://dx.doi.org/10.1158/0008-5472.CAN-13-2409
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000346362400013&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://cancerres.aacrjournals.org/content/74/23/6867
VL  - 74
ER  -
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