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Cancer Prev Res (Phila). 2014 Jul;7(7):748-57. doi: 10.1158/1940-6207.CAPR-14-0057. Epub 2014 May 12.

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

Author information

  • 1Authors' Affiliations: Department of Biochemistry and Cancer Biology, Meharry Medical College; Division of Allergy, Pulmonary and Critical Care Medicine, Departments of.
  • 2Division of Allergy, Pulmonary and Critical Care Medicine, Departments of.
  • 3Biostatistics.
  • 4Pathology, Microbiology and Immunology, and.
  • 5Department of Chemistry, Université de Montréal, Montreal, Quebec, Canada.
  • 6Mass Spectrometry Research Center, Vanderbilt University School of Medicine;
  • 7Molecular Physiology and Biophysics.
  • 8Division of Allergy, Pulmonary and Critical Care Medicine, Departments of Veterans Affairs Medical Center, Nashville, Tennessee; and pierre.massion@vanderbilt.edu.

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.

©2014 American Association for Cancer Research.

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