The airway epithelium undergoes metabolic reprogramming in individuals at high risk for lung cancer.
| Autor: | Rahman SMJ; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Cancer Early Detection and Prevention Initiative, Vanderbilt Ingram Cancer Center., Ji X; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Cancer Early Detection and Prevention Initiative, Vanderbilt Ingram Cancer Center., Zimmerman LJ; Department of Biochemistry., Li M; Department of Biostatistics, and., Harris BK; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Cancer Early Detection and Prevention Initiative, Vanderbilt Ingram Cancer Center., Hoeksema MD; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Cancer Early Detection and Prevention Initiative, Vanderbilt Ingram Cancer Center., Trenary IA; Department of Chemical and Biomolecular Engineering, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Zou Y; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Cancer Early Detection and Prevention Initiative, Vanderbilt Ingram Cancer Center., Qian J; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Cancer Early Detection and Prevention Initiative, Vanderbilt Ingram Cancer Center., Slebos RJ; Department of Biochemistry., Beane J; Pulmonary Center and Section of Computational Biomedicine, Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA., Spira A; Pulmonary Center and Section of Computational Biomedicine, Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA., Shyr Y; Department of Biostatistics, and., Eisenberg R; Departments of Pathology, Microbiology, and Immunology., Liebler DC; Department of Biochemistry., Young JD; Department of Chemical and Biomolecular Engineering, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Department of Molecular Physiology and Biophysics, and., Massion PP; 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. |
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| Jazyk: | angličtina |
| Zdroj: | JCI insight [JCI Insight] 2016 Nov 17; Vol. 1 (19), pp. e88814. Date of Electronic Publication: 2016 Nov 17. |
| DOI: | 10.1172/jci.insight.88814 |
| Abstrakt: | 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- 13 C Competing Interests: The authors have declared that no conflict of interest exists. |
| Databáze: | MEDLINE |
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