title: Deregulated Myc requires MondoA/Mlx for metabolic reprogramming and tumorigenesis.
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.
authors: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, MS A2-025, P.O. Box 19024, Seattle, WA 98109-1024, USA.
authors: Patrick A
authors: PA
authors: Carroll
authors: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, MS A2-025, P.O. Box 19024, Seattle, WA 98109-1024, USA.
authors: Daniel
authors: D
authors: Diolaiti
authors: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, MS A2-025, P.O. Box 19024, Seattle, WA 98109-1024, USA.
authors: Lisa
authors: L
authors: McFerrin
authors: Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington, 850 Republican Street, Room S148, P.O. Box 358057, Seattle, WA 98109-8057, USA.
authors: Haiwei
authors: H
authors: Gu
authors: Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington, 850 Republican Street, Room S148, P.O. Box 358057, Seattle, WA 98109-8057, USA.
authors: Danijel
authors: D
authors: Djukovic
authors: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
authors: Jianhai
authors: J
authors: Du
authors: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, MS A2-025, P.O. Box 19024, Seattle, WA 98109-1024, USA.
authors: Pei Feng
authors: PF
authors: Cheng
authors: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, MS A2-025, P.O. Box 19024, Seattle, WA 98109-1024, USA.
authors: Sarah
authors: S
authors: Anderson
authors: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, MS A2-025, P.O. Box 19024, Seattle, WA 98109-1024, USA.
authors: Michelle
authors: M
authors: Ulrich
authors: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Department of Ophthalmology, University of Washington, Seattle, WA 98195, USA.
authors: James B
authors: JB
authors: Hurley
authors: Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington, 850 Republican Street, Room S148, P.O. Box 358057, Seattle, WA 98109-8057, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Seattle, WA 98109, USA.
authors: Daniel
authors: D
authors: Raftery
authors: Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA.
authors: Donald E
authors: DE
authors: Ayer
authors: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, MS A2-025, P.O. Box 19024, Seattle, WA 98109-1024, USA. Electronic address: eisenman@fhcrc.org.
authors: Robert N
authors: RN
authors: Eisenman
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000737:chemistry / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics; D065150:Cellular Reprogramming / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055503:Protein Multimerization; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C485496:MLXIP protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc
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