Lactate Metabolism in Human Lung Tumors
| Autor: | Christopher T. Hensley, Qing Yuan, Quyen N. Do, Jose R. Torrealba, Hong Li, Jamey D. Young, Kemp H. Kernstine, Jiyeon Kim, Giselle Huet, Robert E. Lenkinski, Brandon Faubert, Daniel Burguete, Dwight H Oliver, Min Ni, Jason W Wachsmann, Lauren G. Zacharias, Kevin Y. Li, Trevor Wigal, Yasmeen M. Butt, Ling Cai, Craig R. Malloy, Ralph J. DeBerardinis, Sarah Doucette, Chendong Yang |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Monocarboxylic Acid Transporters medicine.medical_specialty Lung Neoplasms Metabolite Citric Acid Cycle Carbohydrate metabolism Biology Glyceric Acids General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound Mice Internal medicine Carcinoma Non-Small-Cell Lung Cell Line Tumor medicine Animals Humans Glycolysis Lactic Acid Lung cancer Symporters Metabolism medicine.disease Warburg effect respiratory tract diseases 3. Good health Citric acid cycle Disease Models Animal 030104 developmental biology Endocrinology chemistry Cancer cell Cancer research Heterografts Female Blood Chemical Analysis Neoplasm Transplantation |
| Zdroj: | Cell. 171(2) |
| ISSN: | 1097-4172 |
| Popis: | Summary Cancer cells consume glucose and secrete lactate in culture. It is unknown whether lactate contributes to energy metabolism in living tumors. We previously reported that human non-small-cell lung cancers (NSCLCs) oxidize glucose in the tricarboxylic acid (TCA) cycle. Here, we show that lactate is also a TCA cycle carbon source for NSCLC. In human NSCLC, evidence of lactate utilization was most apparent in tumors with high 18 fluorodeoxyglucose uptake and aggressive oncological behavior. Infusing human NSCLC patients with 13 C-lactate revealed extensive labeling of TCA cycle metabolites. In mice, deleting monocarboxylate transporter-1 (MCT1) from tumor cells eliminated lactate-dependent metabolite labeling, confirming tumor-cell-autonomous lactate uptake. Strikingly, directly comparing lactate and glucose metabolism in vivo indicated that lactate's contribution to the TCA cycle predominates. The data indicate that tumors, including bona fide human NSCLC, can use lactate as a fuel in vivo . |
| Databáze: | OpenAIRE |
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