Supplementary Figure 1 from Blocking Lactate Export by Inhibiting the Myc Target MCT1 Disables Glycolysis and Glutathione Synthesis

Doherty, Joanne R.; Yang, Chunying; Scott, Kristen E.N.; Cameron, Michael D.; Fallahi, Mohammad; Li, Weimin; Hall, Mark A.; Amelio, Antonio L.; Mishra, Jitendra K.; Li, Fangzheng; Tortosa, Mariola; Genau, Heide Marika; Rounbehler, Robert J.; Lu, Yunqi; Dang, Chi V.; Kumar, K. Ganesh; Butler, Andrew A.; Bannister, Thomas D.; Hooper, Andrea T.; Unsal-Kacmaz, Keziban; Roush, William R.; Cleveland, John L.

doi:10.1158/0008-5472.22400960.v1

Supplementary Figure 1 from Blocking Lactate Export by Inhibiting the Myc Target MCT1 Disables Glycolysis and Glutathione Synthesis

journal contribution

posted on 2023-03-30, 22:23 authored by Joanne R. Doherty, Chunying Yang, Kristen E.N. Scott, Michael D. Cameron, Mohammad Fallahi, Weimin Li, Mark A. Hall, Antonio L. Amelio, Jitendra K. Mishra, Fangzheng Li, Mariola Tortosa, Heide Marika Genau, Robert J. Rounbehler, Yunqi Lu, Chi V. Dang, K. Ganesh Kumar, Andrew A. Butler, Thomas D. Bannister, Andrea T. Hooper, Keziban Unsal-Kacmaz, William R. Roush, John L. Cleveland

PDF file - 249K, Expression analysis of glycolytic genes in EMu-Myc B cells and lymphoma versus wild type B cells.

History

ARTICLE ABSTRACT

Myc oncoproteins induce genes driving aerobic glycolysis, including lactate dehydrogenase-A that generates lactate. Here, we report that Myc controls transcription of the lactate transporter SLC16A1/MCT1 and that elevated MCT1 levels are manifest in premalignant and neoplastic Eμ-Myc transgenic B cells and in human malignancies with MYC or MYCN involvement. Notably, disrupting MCT1 function leads to an accumulation of intracellular lactate that rapidly disables tumor cell growth and glycolysis, provoking marked alterations in glycolytic intermediates, reductions in glucose transport, and in levels of ATP, NADPH, and ultimately, glutathione (GSH). Reductions in GSH then lead to increases in hydrogen peroxide, mitochondrial damage, and ultimately, cell death. Finally, forcing glycolysis by metformin treatment augments this response and the efficacy of MCT1 inhibitors, suggesting an attractive combination therapy for MYC/MCT1-expressing malignancies. Cancer Res; 74(3); 908–20. ©2013 AACR.