Lactate metabolism in human lung tumors

By B. Faubert, Kevin Li, L. Cai, C. Hensley, Jiyeon Kim, L. Zacharias, Chendong Yang, Quyen N. Do, Sarah Doucette, Daniel Burguete and 14 more. Cell, 2017

1,193 citations recorded by the source corpus.

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 (NSCLC) 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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/50b51792ceb8df45c394fe450ff6f70e7e15e362

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Citations in the corpus

Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions (2023, background): “Pyruvate is converted from glycolysis to lactate, while lactate is used as a respiratory fuel to support the energy and synthetic functions of the TCA cycle, which is significant for the proliferation of cancer cells.(164)”
Targeting Metabolism to Improve the Tumor Microenvironment for Cancer Immunotherapy. (2020, background): “These data suggest that targeting lactate-responsive pathways or receptors such as GPR81 may provide a promising approach to cancer therapeutics (Faubert et al., 2017).”
Lactate in the Regulation of Tumor Microenvironment and Therapeutic Approaches (2019, background): “(56) showed that the circulatory turnover flux of lactate is the highest of all metabolites and exceeds that of glucose in human lung tumors.”
Metabolic reprogramming and cancer progression (2020, background): “In human lung cancer, infusing patients with (13)C-glucose during surgical resection of their tumors revealed marked regional metabolic heterogeneity despite the presence of truncal mutations in multiple regions (58, 59).”
Metabolomics and isotope tracing (2018, background): “TCA carbon sources [U-(13)C]nutrients Succinate Malate Citrate a-ketoglutarate Carbon enrichment (number of (13)C atoms versus total carbon atoms) reflects carbon contribution from the nutrient; useful in vivowith correction for circulating nutrient enrichment (Davidson et al., 2016; Faubert et al.,”
Class I histone deacetylases (HDAC1–3) are histone lysine delactylases (2021, background): “In these experiments, cells with detectable levels of transfected HDACs 1 and 3 also showed strong reduction of Kac, Kcr, and H4K5la levels, but not for the H3K18la mark or global Kla modification.”
Metabolic reprogramming and epigenetic modifications on the path to cancer (2021, background): “Lactic acid has long been considered a waste product of glycolytic metabolism; however, in 2017, two independent groups recently found that it can be reused as the primary carbon source for the mitochondrial TCA cycle in normal tissues and tumors (Faubert et al., 2017; Hui et al., 2017; Sun et al., ”