TY - JOUR
T1 - Phospholipid profiling identifies acyl chain elongation as a ubiquitous trait and potential target for the treatment of lung squamous cell carcinoma
AU - Marien, Eyra
AU - Meister, Michael
AU - Muley, Thomas
AU - del Pulgar, Teresa Gomez
AU - Derua, Rita
AU - Spraggins, Jeffrey M.
AU - Van De Plas, Raf
AU - Vanderhoydonc, Frank
AU - Machiels, Jelle
AU - Binda, Maria Mercedes
AU - Dehairs, Jonas
AU - Willette-Brown, Jami
AU - Hu, Yinling
AU - Dienemann, Hendrik
AU - Thomas, Michael
AU - Schnabe, Philipp A.
AU - Caprioli, Richard M.
AU - Lacal, Juan Carlos
AU - Waelkens, Etienne
AU - Swinnen, Johannes V.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Cancer
KW - ELOVL
KW - Lipidomics
KW - Lung SCC
KW - Phospholipids
UR - http://resolver.tudelft.nl/uuid:63a66e49-aa59-4773-bccf-de7252d35df0
UR - http://www.scopus.com/inward/record.url?scp=84962802988&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.7179
DO - 10.18632/oncotarget.7179
M3 - Article
AN - SCOPUS:84962802988
SN - 1949-2553
VL - 7
SP - 12582
EP - 12597
JO - OncoTarget
JF - OncoTarget
IS - 11
ER -