Interactions between Myc and MondoA transcription factors in metabolism and tumourigenesis

Br J Cancer. 2015 Dec 1;113(11):1529-33. doi: 10.1038/bjc.2015.360. Epub 2015 Oct 15.

Abstract

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-1α (HIF-1α) 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-1α 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-1α 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Glycolysis* / genetics
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Melanoma / drug therapy
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Neuroblastoma / genetics
  • Neuroblastoma / metabolism*
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / metabolism*

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Carrier Proteins
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MONDOA protein, human
  • Proto-Oncogene Proteins c-myc
  • TXNIP protein, human
  • Transcription Factors