title: The airway epithelium undergoes metabolic reprogramming in individuals at high risk for lung cancer.
abstract: The molecular determinants of lung cancer risk remain largely unknown. Airway epithelial cells are prone to assault by risk factors and are considered to be the primary cell type involved in the field of cancerization. To investigate risk-associated changes in the bronchial epithelium proteome that may offer new insights into the molecular pathogenesis of lung cancer, proteins were identified in the airway epithelial cells of bronchial brushing specimens from risk-stratified individuals by shotgun proteomics. Differential expression of selected proteins was validated by parallel reaction monitoring mass spectrometry in an independent set of individual bronchial brushings. We identified 2,869 proteins, of which 312 proteins demonstrated a trend in expression. Pathway analysis revealed enrichment of carbohydrate metabolic enzymes in high-risk individuals. Glucose consumption and lactate production were increased in human bronchial epithelial BEAS2B cells treated with cigarette smoke condensate for 7 months. Increased lipid biosynthetic capacity and net reductive carboxylation were revealed by metabolic flux analyses of [U-13C5] glutamine in this in vitro model, suggesting profound metabolic reprogramming in the airway epithelium of high-risk individuals. These results provide a rationale for the development of potentially new chemopreventive strategies and selection of patients for surveillance programs.
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Cancer Early Detection and Prevention Initiative, Vanderbilt Ingram Cancer Center.
authors.forename: S M Jamshedur
authors.initials: SMJ
authors.lastname: Rahman
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Cancer Early Detection and Prevention Initiative, Vanderbilt Ingram Cancer Center.
authors.forename: Xiangming
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Biochemistry.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Zimmerman
authors.affiliation: Department of Biostatistics, and.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Cancer Early Detection and Prevention Initiative, Vanderbilt Ingram Cancer Center.
authors.forename: Bradford K
authors.initials: BK
authors.lastname: Harris
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Cancer Early Detection and Prevention Initiative, Vanderbilt Ingram Cancer Center.
authors.forename: Megan D
authors.initials: MD
authors.lastname: Hoeksema
authors.affiliation: Department of Chemical and Biomolecular Engineering, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Trenary
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Cancer Early Detection and Prevention Initiative, Vanderbilt Ingram Cancer Center.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Cancer Early Detection and Prevention Initiative, Vanderbilt Ingram Cancer Center.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of Biochemistry.
authors.forename: Robbert Jc
authors.initials: RJ
authors.lastname: Slebos
authors.affiliation: Pulmonary Center and Section of Computational Biomedicine, Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Beane
authors.affiliation: Pulmonary Center and Section of Computational Biomedicine, Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA.
authors.forename: Avrum
authors.initials: A
authors.lastname: Spira
authors.affiliation: Department of Biostatistics, and.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shyr
authors.affiliation: Departments of Pathology, Microbiology, and Immunology.
authors.forename: Rosana
authors.initials: R
authors.lastname: Eisenberg
authors.affiliation: Department of Biochemistry.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Liebler
authors.affiliation: Department of Chemical and Biomolecular Engineering, Vanderbilt University Medical Center, Nashville, Tennessee, USA.|Department of Molecular Physiology and Biophysics, and.
authors.forename: Jamey D
authors.initials: JD
authors.lastname: Young
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Cancer Early Detection and Prevention Initiative, Vanderbilt Ingram Cancer Center.|Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.|Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA.
authors.forename: Pierre P
authors.initials: PP
authors.lastname: Massion
mesh_terms: D001980:Bronchi; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D050356:Lipid Metabolism; D008175:Lung Neoplasms / Q000378:metabolism; D055432:Metabolomics; D020543:Proteome / Q000032:analysis*; D020545:Respiratory Mucosa / Q000166:cytology / Q000473:pathology*; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking
chemical_list: D020543:Proteome; D012906:Smoke