Title
Phospholipid profiling identifies acyl chain elongation as a ubiquitous trait and potential target for the treatment of lung squamous cell carcinoma
Author
Marien, Eyra (Katholieke Universiteit Leuven)
Meister, Michael (Heidelberg University Hospital)
Muley, Thomas (Heidelberg University Hospital)
del Pulgar, Teresa Gomez (Division of Translational Oncology)
Derua, Rita (Katholieke Universiteit Leuven)
Spraggins, Jeffrey M. (Mass Spectrometry Research Center)
Van de Plas, Raf (TU Delft Team Raf Van de Plas; VanderBilt University) 
Vanderhoydonc, Frank (Katholieke Universiteit Leuven)
Machiels, Jelle (Katholieke Universiteit Leuven)
Binda, Maria Mercedes (Katholieke Universiteit Leuven)
Dehairs, Jonas (Katholieke Universiteit Leuven)
Willette-Brown, Jami (National Cancer Institute)
Hu, Yinling (National Cancer Institute)
Dienemann, Hendrik (Member of the German Center for Lung Research; Heidelberg University Hospital)
Thomas, Michael (Member of the German Center for Lung Research; Heidelberg University Hospital)
Schnabe, Philipp A. (Member of the German Center for Lung Research; Saarland University)
Caprioli, Richard M. (Mass Spectrometry Research Center)
Lacal, Juan Carlos (Division of Translational Oncology)
Waelkens, Etienne (Katholieke Universiteit Leuven)
Swinnen, Johannes V. (Katholieke Universiteit Leuven)
Date
2016
Abstract
Lung cancer is the leading cause of cancer death. Beyond first line treatment, few therapeutic options are available, particularly for squamous cell carcinoma (SCC). Here, we have explored the phospholipidomes of 30 human SCCs and found that they almost invariably (in 96.7% of cases) contain phospholipids with longer acyl chains compared to matched normal tissues. This trait was confirmed using in situ 2D-imaging MS on tissue sections and by phospholipidomics of tumor and normal lung tissue of the L-IkkaKA/KA mouse model of lung SCC. In both human and mouse, the increase in acyl chain length in cancer tissue was accompanied by significant changes in the expression of acyl chain elongases (ELOVLs). Functional screening of differentially expressed ELOVLs by selective gene knockdown in SCC cell lines followed by phospholipidomics revealed ELOVL6 as the main elongation enzyme responsible for acyl chain elongation in cancer cells. Interestingly, inhibition of ELOVL6 drastically reduced colony formation of multiple SCC cell lines in vitro and significantly attenuated their growth as xenografts in vivo in mouse models. These findings identify acyl chain elongation as one of the most common traits of lung SCC discovered so far and pinpoint ELOVL6 as a novel potential target for cancer intervention.
Subject
Cancer
ELOVL
Lipidomics
Lung SCC
Phospholipids
To reference this document use:
http://resolver.tudelft.nl/uuid:63a66e49-aa59-4773-bccf-de7252d35df0
DOI
https://doi.org/10.18632/oncotarget.7179
Source
OncoTarget, 7 (11), 12582-12597
Part of collection
Institutional Repository
Document type
journal article
Rights
© 2016 Eyra Marien, Michael Meister, Thomas Muley, Teresa Gomez del Pulgar, Rita Derua, Jeffrey M. Spraggins, Raf Van de Plas, Frank Vanderhoydonc, Jelle Machiels, Maria Mercedes Binda, Jonas Dehairs, Jami Willette-Brown, Yinling Hu, Hendrik Dienemann, Michael Thomas, Philipp A. Schnabe, Richard M. Caprioli, Juan Carlos Lacal, Etienne Waelkens, Johannes V. Swinnen