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
Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA; Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Cell. 2017 Oct 5;171(2):358-371.e9. doi: 10.1016/j.cell.2017.09.019.
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 fluorodeoxyglucose uptake and aggressive oncological behavior. Infusing human NSCLC patients with C-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.
癌细胞在培养过程中消耗葡萄糖并分泌乳酸。目前尚不清楚乳酸是否有助于活体肿瘤中的能量代谢。我们之前报道过人非小细胞肺癌（NSCLC）在三羧酸（TCA）循环中氧化葡萄糖。在此，我们表明乳酸也是NSCLC的TCA循环碳源。在人NSCLC中，乳酸利用的证据在氟脱氧葡萄糖摄取高且具有侵袭性肿瘤行为的肿瘤中最为明显。给人NSCLC患者输注¹³C-乳酸显示TCA循环代谢物有广泛标记。在小鼠中，从肿瘤细胞中删除单羧酸转运蛋白-1（MCT1）消除了乳酸依赖性代谢物标记，证实了肿瘤细胞自主摄取乳酸。令人惊讶的是，在体内直接比较乳酸和葡萄糖代谢表明，乳酸对TCA循环的贡献占主导。数据表明，包括真正的人NSCLC在内的肿瘤在体内可以将乳酸用作燃料。
