Lactate Metabolism in Human Lung Tumors

Brandon Faubert, Kevin Y. Li, Ling Cai, Christopher T. Hensley, Jiyeon Kim, Lauren G. Zacharias, Chendong Yang, Quyen N. Do, Sarah Doucette, Daniel Burguete, Hong Li, Giselle Huet, Qing Yuan, Trevor Wigal, Yasmeen Butt, Min Ni, Jose Torrealba, Dwight Oliver, Robert E. Lenkinski, Craig R. MalloyJason W. Wachsmann, Jamey D. Young, Kemp Kernstine, Ralph J. DeBerardinis

Research output: Contribution to journalArticle

243 Scopus citations

Abstract

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 18fluorodeoxyglucose uptake and aggressive oncological behavior. Infusing human NSCLC patients with 13C-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. Human non-small cell lung cancer preferentially utilizes lactate over glucose to fuel TCA cycle and sustain tumor metabolism in vivo.

Original languageEnglish (US)
Pages (from-to)358-371.e9
JournalCell
Volume171
Issue number2
DOIs
StatePublished - Oct 5 2017

Keywords

  • Cancer metabolism
  • Glycolysis
  • Lactate
  • Lung cancer
  • Metabolic flux analysis
  • Monocarboxylate transport
  • Tricarboxylic Acid Cycle
  • Warburg effect

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Faubert, B., Li, K. Y., Cai, L., Hensley, C. T., Kim, J., Zacharias, L. G., Yang, C., Do, Q. N., Doucette, S., Burguete, D., Li, H., Huet, G., Yuan, Q., Wigal, T., Butt, Y., Ni, M., Torrealba, J., Oliver, D., Lenkinski, R. E., ... DeBerardinis, R. J. (2017). Lactate Metabolism in Human Lung Tumors. Cell, 171(2), 358-371.e9. https://doi.org/10.1016/j.cell.2017.09.019