Deregulated Myc Requires MondoAMlx for Metabolic Reprogramming and Tumorigenesis

Deregulated Myc 1 groupedDeregulated 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.

Here we show that MondoA loss suppresses Myc-induced GLN uptake, GLN-dependent mitochondrial activity and Gln-derived lipid biosynthesis, thus resulting in apoptosis. Identification, and knockdown, of genes co-regulated by Myc and MondoA has 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 co-regulated genes correlates with poor outcome of patients with diverse cancers. Co-regulation of cancer metabolism by Myc and MondoA provides the potential for therapeutics aimed at inhibiting MondoA and its target genes.

Citation & Full Text

Carroll, P., Diolaiti, D., McFerrin, L., Gu, H., Djukovic, D., Du, D., Cheng, P.F., Anderson, S., Ulrich, M., Hurley, J.B., Raftery, D., Ayer, D.E., Eisenman, R.N.: Deregulated Myc Requires MondoA/Mlx for Metabolic Reprogramming and Tumorigenesis. Cancer Cell 27:271-285, 2015. PMCID: PMC4326605.