139 Citations (Scopus)

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

Fingerprint

Metabolism
Tumors
Lactic Acid
Lung
Citric Acid Cycle
Non-Small Cell Lung Carcinoma
Cells
Neoplasms
Glucose
Metabolites
Labeling
Cell culture
Energy Metabolism
Carbon

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)

Cite this

Faubert, B., Li, K. Y., Cai, L., Hensley, C. T., Kim, J., Zacharias, L. G., ... 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

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

In: Cell, Vol. 171, No. 2, 05.10.2017, p. 358-371.e9.

Research output: Contribution to journalArticle

Faubert, B, Li, KY, Cai, L, Hensley, CT, Kim, J, Zacharias, LG, Yang, C, Do, QN, Doucette, S, Burguete, D, Li, H, Huet, G, Yuan, Q, Wigal, T, Butt, Y, Ni, M, Torrealba, J, Oliver, D, Lenkinski, RE, Malloy, CR, Wachsmann, JW, Young, JD, Kernstine, K & DeBerardinis, RJ 2017, 'Lactate Metabolism in Human Lung Tumors', Cell, vol. 171, no. 2, pp. 358-371.e9. https://doi.org/10.1016/j.cell.2017.09.019
Faubert B, Li KY, Cai L, Hensley CT, Kim J, Zacharias LG et al. Lactate Metabolism in Human Lung Tumors. Cell. 2017 Oct 5;171(2):358-371.e9. https://doi.org/10.1016/j.cell.2017.09.019
Faubert, Brandon ; Li, Kevin Y. ; Cai, Ling ; Hensley, Christopher T. ; Kim, Jiyeon ; Zacharias, Lauren G. ; Yang, Chendong ; Do, Quyen N. ; Doucette, Sarah ; Burguete, Daniel ; Li, Hong ; Huet, Giselle ; Yuan, Qing ; Wigal, Trevor ; Butt, Yasmeen ; Ni, Min ; Torrealba, Jose ; Oliver, Dwight ; Lenkinski, Robert E. ; Malloy, Craig R. ; Wachsmann, Jason W. ; Young, Jamey D. ; Kernstine, Kemp ; DeBerardinis, Ralph J. / Lactate Metabolism in Human Lung Tumors. In: Cell. 2017 ; Vol. 171, No. 2. pp. 358-371.e9.
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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.",
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AU - Li, Kevin Y.

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AU - Zacharias, Lauren G.

AU - Yang, Chendong

AU - Do, Quyen N.

AU - Doucette, Sarah

AU - Burguete, Daniel

AU - Li, Hong

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AU - Torrealba, Jose

AU - Oliver, Dwight

AU - Lenkinski, Robert E.

AU - Malloy, Craig R.

AU - Wachsmann, Jason W.

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AU - Kernstine, Kemp

AU - DeBerardinis, Ralph J.

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N2 - 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.

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