@article{22e77b6ef12e4a48b3ad058a57d53ff0,
title = "Lactate Metabolism in Human Lung Tumors",
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.",
keywords = "Cancer metabolism, Glycolysis, Lactate, Lung cancer, Metabolic flux analysis, Monocarboxylate transport, Tricarboxylic Acid Cycle, Warburg effect",
author = "Brandon Faubert and Li, {Kevin Y.} and Ling Cai and Hensley, {Christopher T.} and Jiyeon Kim and Zacharias, {Lauren G.} and Chendong Yang and Do, {Quyen N.} and Sarah Doucette and Daniel Burguete and Hong Li and Giselle Huet and Qing Yuan and Trevor Wigal and Yasmeen Butt and Min Ni and Jose Torrealba and Dwight Oliver and Lenkinski, {Robert E.} and Malloy, {Craig R.} and Wachsmann, {Jason W.} and Young, {Jamey D.} and Kemp Kernstine and DeBerardinis, {Ralph J.}",
note = "Funding Information: We thank the DeBerardinis lab and Aron Jaffe for helpful discussions. B.F. is supported by the Canadian Institutes of Health Research ( MFE 140911 ). J.K. is supported by an American Lung Association Fellowship ( RT-306212 ). J.D.Y. is supported by NIH grant R01 DK106348 . R.J.D. is supported by grants from the NIH ( R35CA220449 ), Howard Hughes Medical Institute (Faculty Scholars Program, grant 55108514 ), the Welch Foundation ( I-1733 ), and the V Foundation (Translational Award). We acknowledge support from NIH grants P50 CA70907 , P41 EB015908 , and UL1 TR001105 and from the UT Southwestern Small Animal Imaging Resource, which is supported in part through an NCI Cancer Center Support Grant ( 1P30 CA142543-01 ). R.E.L. is the recipient of a research grant from Philips Healthcare . R.J.D. is an advisor for Agios Pharmaceuticals. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = oct,
day = "5",
doi = "10.1016/j.cell.2017.09.019",
language = "English (US)",
volume = "171",
pages = "358--371.e9",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",
}