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The airway epithelium undergoes metabolic reprogramming in individuals at high risk for lung cancer
S.M. Jamshedur Rahman, … , Jamey D. Young, Pierre P. Massion
S.M. Jamshedur Rahman, … , Jamey D. Young, Pierre P. Massion
Published November 17, 2016
Citation Information: JCI Insight. 2016;1(19):e88814. https://doi.org/10.1172/jci.insight.88814.
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Research Article Metabolism Oncology

The airway epithelium undergoes metabolic reprogramming in individuals at high risk for lung cancer

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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

S.M. Jamshedur Rahman, Xiangming Ji, Lisa J. Zimmerman, Ming Li, Bradford K. Harris, Megan D. Hoeksema, Irina A. Trenary, Yong Zou, Jun Qian, Robbert J.C. Slebos, Jennifer Beane, Avrum Spira, Yu Shyr, Rosana Eisenberg, Daniel C. Liebler, Jamey D. Young, Pierre P. Massion

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Figure 1

Proteomic changes in carbohydrate metabolic enzyme expression in the bronchial brushings of individuals at high risk for lung cancer.

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Proteomic changes in carbohydrate metabolic enzyme expression in the bro...
All enzymes shown as gene symbols (blue and red) were detected by shotgun proteomic (LC-MS/MS) analysis of cytologically normal airway epithelial cells from individuals at low, medium, and high risk for lung cancer. Equal amounts of protein (20 μg) were pooled from each bronchial brushing lysate of each of the low-risk (n = 5), medium-risk (n = 5), and high-risk (n = 5) groups to create a 100-μg pooled protein lysate. Jonckheere-Terpstra trend analysis was performed with the risk groups using normalized spectral count obtained from LC-MS/MS data. Gene symbols of overexpressed enzymes are shown in red and gene symbols shown in blue are not overexpressed. Jonckheere-Terpstra trend analysis was performed with the risk groups using normalized spectral count obtained from LC-MS/MS data.

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