title: Phospholipid profiling identifies acyl chain elongation as a ubiquitous trait and potential target for the treatment of lung squamous cell carcinoma.
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-IkkαKA/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.
authors: KU Leuven - University of Leuven, LKI - Leuven Cancer Institute, Department of Oncology, Laboratory of Lipid Metabolism and Cancer, Leuven, Belgium.
authors: Eyra
authors: E
authors: Marien
authors: Thoraxklinik at University Hospital Heidelberg, Translational Research Unit, Heidelberg, Germany.|TLRC-H - Translational Lung Research Center Heidelberg, Member of The German Center for Lung Research, Heidelberg, Germany.
authors: Michael
authors: M
authors: Meister
authors: Thoraxklinik at University Hospital Heidelberg, Translational Research Unit, Heidelberg, Germany.|TLRC-H - Translational Lung Research Center Heidelberg, Member of The German Center for Lung Research, Heidelberg, Germany.
authors: Thomas
authors: T
authors: Muley
authors: Fundación Jiménez Díaz, Division of Translational Oncology, Madrid, Spain.
authors: Teresa
authors: T
authors: Gomez Del Pulgar
authors: KU Leuven - University of Leuven, Department of Cellular and Molecular Medicine, Laboratory of Protein Phosphorylation and Proteomics, Leuven, Belgium.
authors: Rita
authors: R
authors: Derua
authors: Vanderbilt University Medical Center, Department of Biochemistry and Mass Spectrometry Research Center, Nashville, TN, USA.
authors: Jeffrey M
authors: JM
authors: Spraggins
authors: Vanderbilt University Medical Center, Department of Biochemistry and Mass Spectrometry Research Center, Nashville, TN, USA.|Delft University of Technology, Delft Center for Systems and Control, Delft, The Netherlands.
authors: Raf
authors: R
authors: Van de Plas
authors: KU Leuven - University of Leuven, LKI - Leuven Cancer Institute, Department of Oncology, Laboratory of Lipid Metabolism and Cancer, Leuven, Belgium.
authors: Frank
authors: F
authors: Vanderhoydonc
authors: KU Leuven - University of Leuven, LKI - Leuven Cancer Institute, Department of Oncology, Laboratory of Lipid Metabolism and Cancer, Leuven, Belgium.
authors: Jelle
authors: J
authors: Machiels
authors: KU Leuven - University of Leuven, LKI - Leuven Cancer Institute, Department of Oncology, Abdominal Surgical Oncology, Leuven, Belgium.
authors: Maria Mercedes
authors: MM
authors: Binda
authors: KU Leuven - University of Leuven, LKI - Leuven Cancer Institute, Department of Oncology, Laboratory of Lipid Metabolism and Cancer, Leuven, Belgium.
authors: Jonas
authors: J
authors: Dehairs
authors: National Cancer Institute, Centre for Cancer Research, Cancer and Inflammation Program, Frederick, MD, USA.
authors: Jami
authors: J
authors: Willette-Brown
authors: National Cancer Institute, Centre for Cancer Research, Cancer and Inflammation Program, Frederick, MD, USA.
authors: Yinling
authors: Y
authors: Hu
authors: TLRC-H - Translational Lung Research Center Heidelberg, Member of The German Center for Lung Research, Heidelberg, Germany.|Thoraxklinik at University Hospital Heidelberg, Department of Surgery, Heidelberg, Germany.
authors: Hendrik
authors: H
authors: Dienemann
authors: TLRC-H - Translational Lung Research Center Heidelberg, Member of The German Center for Lung Research, Heidelberg, Germany.|Thoraxklinik at University Hospital Heidelberg, Department of Thoracic Oncology, Heidelberg, Germany.
authors: Michael
authors: M
authors: Thomas
authors: TLRC-H - Translational Lung Research Center Heidelberg, Member of The German Center for Lung Research, Heidelberg, Germany.|University of The Saarland, Institut für Allgemeine und Spezielle Pathologie, Homburg/Saar, Germany.
authors: Philipp A
authors: PA
authors: Schnabel
authors: Vanderbilt University Medical Center, Department of Biochemistry and Mass Spectrometry Research Center, Nashville, TN, USA.
authors: Richard M
authors: RM
authors: Caprioli
authors: Fundación Jiménez Díaz, Division of Translational Oncology, Madrid, Spain.
authors: Juan Carlos
authors: JC
authors: Lacal
authors: KU Leuven - University of Leuven, Department of Cellular and Molecular Medicine, Laboratory of Protein Phosphorylation and Proteomics, Leuven, Belgium.
authors: Etienne
authors: E
authors: Waelkens
authors: KU Leuven - University of Leuven, LKI - Leuven Cancer Institute, Department of Oncology, Laboratory of Lipid Metabolism and Cancer, Leuven, Belgium.
authors: Johannes V
authors: JV
authors: Swinnen
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000737:chemistry; D000081031:Fatty Acid Elongases; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry; D051379:Mice; D010743:Phospholipids / Q000737:chemistry*
chemical_list: C000630955:ELOVL6 protein, human; C000630968:Elovl6 protein, mouse; D010743:Phospholipids; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases
keywords: ELOVL; cancer; lipidomics; lung SCC; phospholipids