Acyl-coenzyme A-binding protein regulates Beta-oxidation required for growth and survival of non-small cell lung cancer.

Harris FT, Rahman SM, Hassanein M, Qian J, Hoeksema MD, Chen H, Eisenberg R, Chaurand P, Caprioli RM, Shiota M, Massion PP
Cancer Prev Res (Phila). 2014 7 (7): 748-57

PMID: 24819876 · PMCID: PMC4090029 · DOI:10.1158/1940-6207.CAPR-14-0057

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.

©2014 American Association for Cancer Research.

MeSH Terms (19)

Acetyl Coenzyme A Adenocarcinoma Adenosine Triphosphate Apoptosis Blotting, Western Bronchi Carcinoma, Non-Small-Cell Lung Carcinoma, Squamous Cell Carcinoma in Situ Cell Proliferation Cells, Cultured Diazepam Binding Inhibitor Humans Immunoenzyme Techniques Lung Neoplasms Membrane Potential, Mitochondrial Oxidation-Reduction Palmitic Acid Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

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