title: Acyl-coenzyme A-binding protein regulates Beta-oxidation required for growth and survival of non-small cell lung cancer.
abstract: We identified acyl-coenzyme A-binding protein (ACBP) as part of a proteomic signature predicting the risk of having lung cancer. Because ACBP is known to regulate β-oxidation, which in turn controls cellular proliferation, we hypothesized that ACBP contributes to regulation of cellular proliferation and survival of non-small cell lung cancer (NSCLC) by modulating β-oxidation. We used matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS) and immunohistochemistry (IHC) to confirm the tissue localization of ABCP in pre-invasive and invasive NSCLCs. We correlated ACBP gene expression levels in NSCLCs with clinical outcomes. In loss-of-function studies, we tested the effect of the downregulation of ACBP on cellular proliferation and apoptosis in normal bronchial and NSCLC cell lines. Using tritiated-palmitate ((3)H-palmitate), we measured β-oxidation levels and tested the effect of etomoxir, a β-oxidation inhibitor, on proliferation and apoptosis. MALDI-IMS and IHC analysis confirmed that ACBP is overexpressed in pre-invasive and invasive lung cancers. High ACBP gene expression levels in NSCLCs correlated with worse survival (HR = 1.73). We observed a 40% decrease in β-oxidation and concordant decreases in proliferation and increases in apoptosis in ACBP-depleted NSCLC cells as compared with bronchial airway epithelial cells. Inhibition of β-oxidation by etomoxir in ACBP-overexpressing cells produced dose-dependent decrease in proliferation and increase in apoptosis (P = 0.01 and P < 0.001, respectively). These data suggest a role for ACBP in controlling lung cancer progression by regulating β-oxidation.
authors.affiliation: Authors' Affiliations: Department of Biochemistry and Cancer Biology, Meharry Medical College; Division of Allergy, Pulmonary and Critical Care Medicine, Departments of.
authors.forename: Fredrick T
authors.initials: FT
authors.lastname: Harris
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Departments of.
authors.forename: S M Jamshedur
authors.initials: SM
authors.lastname: Rahman
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Departments of.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hassanein
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Departments of.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Departments of.
authors.forename: Megan D
authors.initials: MD
authors.lastname: Hoeksema
authors.affiliation: Biostatistics.
authors.forename: Heidi
authors.initials: H
authors.lastname: Chen
authors.affiliation: Pathology, Microbiology and Immunology, and.
authors.forename: Rosana
authors.initials: R
authors.lastname: Eisenberg
authors.affiliation: Department of Chemistry, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Chaurand
authors.affiliation: Mass Spectrometry Research Center, Vanderbilt University School of Medicine;
authors.forename: Richard M
authors.initials: RM
authors.lastname: Caprioli
authors.affiliation: Molecular Physiology and Biophysics.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Shiota
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Departments of Veterans Affairs Medical Center, Nashville, Tennessee; and pierre.massion@vanderbilt.edu.
authors.forename: Pierre P
authors.initials: PP
authors.lastname: Massion
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis; D015153:Blotting, Western; D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D002278:Carcinoma in Situ / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D026261:Diazepam Binding Inhibitor / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D053078:Membrane Potential, Mitochondrial; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D026261:Diazepam Binding Inhibitor; D019308:Palmitic Acid; D000105:Acetyl Coenzyme A; D000255:Adenosine Triphosphate