Document Type
Article
Journal Title
Nature Communications
Publication Date
2017
Volume
8
Abstract
Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, while lung ADC exhibits significant glucose independence. Clinically, elevated GLUT1-mediated glycolysis in lung SqCC strongly correlates with high 18F-FDG uptake and poor prognosis. This previously undescribed metabolic heterogeneity of NSCLC subtypes implicates significant potential for the development of diagnostic, prognostic and targeted therapeutic strategies for lung SqCC, a cancer for which existing therapeutic options are clinically insufficient.
MeSH Headings
Adenocarcinoma, Adenocarcinoma of Lung, Adult, Aged, Aged, 80 and over, Animals, Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell, Cell Line, Tumor, Cohort Studies, Deoxyglucose, Female, Fluorodeoxyglucose F18, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Glucose, Glucose Transporter Type 1, Glycolysis, Humans, Hydroxybenzoates, Lung, Lung Neoplasms, Male, Mice, Mice, Nude, Middle Aged, Phenotype, Positron-Emission Tomography, Prognosis, Survival Analysis, Up-Regulation, Xenograft Model Antitumor Assays
DOI Link
ISSN
2041-1723
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Goodwin, Justin; Neugent, Michael L.; Lee, Shin Yup; Choe, Joshua H.; Choi, Hyunsung; Jenkins, Dana M. R.; Ruthenborg, Robin J.; Robinson, Maddox W.; Jeong, Ji Yun; Wake, Masaki; Abe, Hajime; Takeda, Norihiko; Endo, Hiroko; Inoue, Masahiro; Xuan, Zhenyu; Yoo, Hyuntae; Chen, Min; Ahn, Jung-Mo; Minna, John D.; Helke, Kristi L.; Singh, Pankaj K.; Shackelford, David B.; and Kim, Jung-Whan, "The Distinct Metabolic Phenotype of Lung Squamous Cell Carcinoma Defines Selective Vulnerability to Glycolytic Inhibition" (2017). Journal Articles: Eppley Institute. 37.
https://digitalcommons.unmc.edu/eppley_articles/37