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 language | English (US) |
|---|---|
| Pages (from-to) | 358-371.e9 |
| Journal | Cell |
| Volume | 171 |
| Issue number | 2 |
| DOIs | |
| State | Published - Oct 5 2017 |
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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
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 journal › Article
}
TY - JOUR
T1 - Lactate Metabolism in Human Lung Tumors
AU - Faubert, Brandon
AU - Li, Kevin Y.
AU - Cai, Ling
AU - Hensley, Christopher T.
AU - Kim, Jiyeon
AU - Zacharias, Lauren G.
AU - Yang, Chendong
AU - Do, Quyen N.
AU - Doucette, Sarah
AU - Burguete, Daniel
AU - Li, Hong
AU - Huet, Giselle
AU - Yuan, Qing
AU - Wigal, Trevor
AU - Butt, Yasmeen
AU - Ni, Min
AU - Torrealba, Jose
AU - Oliver, Dwight
AU - Lenkinski, Robert E.
AU - Malloy, Craig R.
AU - Wachsmann, Jason W.
AU - Young, Jamey D.
AU - Kernstine, Kemp
AU - DeBerardinis, Ralph J.
PY - 2017/10/5
Y1 - 2017/10/5
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.
AB - 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.
KW - Cancer metabolism
KW - Glycolysis
KW - Lactate
KW - Lung cancer
KW - Metabolic flux analysis
KW - Monocarboxylate transport
KW - Tricarboxylic Acid Cycle
KW - Warburg effect
UR - http://www.scopus.com/inward/record.url?scp=85030560166&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85030560166&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2017.09.019
DO - 10.1016/j.cell.2017.09.019
M3 - Article
VL - 171
SP - 358-371.e9
JO - Cell
JF - Cell
SN - 0092-8674
IS - 2
ER -