Rethinking the Warburg Effect with Myc Micromanaging Glutamine Metabolism

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Abstract
The MYC oncogene, which is frequently deregulated in human cancers, encodes a master transcription factor c-Myc (herein termed Myc) that integrates cell proliferation with metabolism through its regulation of thousands of genes including microRNAs (miRNA). In addition to its known function in regulating the cell cycle and glucose metabolism, recent studies document a role for Myc in stimulating glutamine catabolism, in part through the repression of miRNAs miR-23a and miR-23b. These observations suggest an additional level of complexity in tumor metabolism, which includes the commensal metabolic relationship between hypoxic and nonhypoxic regions of tumors as well as the surrounding stroma. Thus, a reevaluation of cancer metabolism considering glutamine catabolism with a better understanding of the tumor histological complexity is needed before cancer metabolism can be effectively targeted in therapy. Cancer Res; 70(3); 859–62