Deregulated Myc Requires MondoA/Mlx for Metabolic Reprogramming and Tumorigenesis

Patrick A. Carroll, Daniel Diolaiti, Lisa McFerrin, Haiwei Gu, Danijel Djukovic, Jianhai Du, Pei Feng Cheng, Sarah Anderson, Michelle Ulrich, James B. Hurley, Daniel Raftery, Donald E. Ayer, Robert N. Eisenman

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

Deregulated Myc transcriptionally reprograms cell metabolism to promote neoplasia. Here we show that oncogenic Myc requires the Myc superfamily member MondoA, a nutrient-sensing transcription factor, for tumorigenesis. Knockdown of MondoA, or its dimerization partner Mlx, blocks Myc-induced reprogramming of multiple metabolic pathways, resulting in apoptosis. Identification and knockdown of genes coregulated by Myc and MondoA have allowed us to define metabolic functions required by deregulated Myc and demonstrate a critical role for lipid biosynthesis in survival of Myc-driven cancer. Furthermore, overexpression of a subset of Myc and MondoA coregulated genes correlates with poor outcome of patients with diverse cancers. Coregulation of cancer metabolism by Myc and MondoA provides the potential for therapeutics aimed at inhibiting MondoA and its target genes.

Original languageEnglish (US)
Pages (from-to)271-285
Number of pages15
JournalCancer cell
Volume27
Issue number2
DOIs
StatePublished - Feb 9 2015
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Carroll, P. A., Diolaiti, D., McFerrin, L., Gu, H., Djukovic, D., Du, J., Cheng, P. F., Anderson, S., Ulrich, M., Hurley, J. B., Raftery, D., Ayer, D. E., & Eisenman, R. N. (2015). Deregulated Myc Requires MondoA/Mlx for Metabolic Reprogramming and Tumorigenesis. Cancer cell, 27(2), 271-285. https://doi.org/10.1016/j.ccell.2014.11.024