Blocking lactate export by inhibiting the Myc target MCT1 Disables glycolysis and glutathione synthesis.
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ABSTRACT:
SUBMITTER: Doherty JR
PROVIDER: S-EPMC3946415 | biostudies-literature | 2014 Feb
REPOSITORIES: biostudies-literature
Publications
Blocking lactate export by inhibiting the Myc target MCT1 Disables glycolysis and glutathione synthesis.
Doherty Joanne R JR Yang Chunying C Scott Kristen E N KE Cameron Michael D MD Fallahi Mohammad M Li Weimin W Hall Mark A MA Amelio Antonio L AL Mishra Jitendra K JK Li Fangzheng F Tortosa Mariola M Genau Heide Marika HM Rounbehler Robert J RJ Lu Yunqi Y Dang Chi V CV Kumar K Ganesh KG Butler Andrew A AA Bannister Thomas D TD Hooper Andrea T AT Unsal-Kacmaz Keziban K Roush William R WR Cleveland John L JL
Cancer research 20131127 3
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, ...[more]
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