Deregulated Myc requires MondoA/Mlx for metabolic reprogramming and tumorigenesis.

Publication Type:

Journal Article

Source:

Cancer cell, Volume 27, Issue 2, p.271-85 (2015)

Keywords:

Animals, APOPTOSIS, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Bioinformatics Core Facility, CARCINOGENESIS, Cellular Reprogramming, Comparative Medicine Core Facility, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Genomics Core Facility, Humans, MICE, Neuroblastoma, Protein Multimerization, Proto-Oncogene Proteins c-myc, Scientific Imaging Core Facility, Xenograft Model Antitumor Assays

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.