Journal
BRITISH JOURNAL OF CANCER
Volume 113, Issue 11, Pages 1529-1533Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2015.360
Keywords
Myc; MondoA; cancer metabolism; transcription; TXNIP; tumourigenesis
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Funding
- Department of Defense [R01GM055668, W81XWH1410445]
- U.S. Department of Defense (DOD) [W81XWH1410445] Funding Source: U.S. Department of Defense (DOD)
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Metabolic reprogramming towards aerobic glycolysis is a common feature of transformed cells and can be driven by a network of transcription factors. It is well established that c-Myc and hypoxia-inducible factor-1 alpha (HIF-1 alpha) contribute to metabolic reprogramming by driving the expression of glycolytic target genes. More recently, the c-Myc-related transcription factor MondoA has been shown to restrict glucose uptake and aerobic glycolysis via its induction of thioredoxin-interacting protein (TXNIP). Three recent studies demonstrate that complex and cancer type-specific interactions between c-Myc, MondoA and HIF-1 alpha underlie metabolism, tumourigenesis and drug response. In triple-negative breast cancer, c-Myc blocks MondoA-dependent activation of TXNIP to stimulate aerobic glycolysis. In contrast, in neuroblastoma, N-Myc requires MondoA for metabolic reprogramming and tumourigenesis. Finally, the therapeutic response of BRAF(V600E) melanoma cells to vemurafenib requires downregulation of c-Myc and HIF-1 alpha and upregulation of MondoA-TXNIP, and the subsequent reprogramming away from aerobic glycolysis. In this minireview we highlight the findings in these three studies and present a working model to explain why c-Myc and MondoA function cooperatively in some cancers and antagonistically in others.
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