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Deregulated Myc requires MondoA/Mlx for metabolic reprogramming and tumorigenesis.
Carroll, Patrick A; Diolaiti, Daniel; McFerrin, Lisa; Gu, Haiwei; Djukovic, Danijel; Du, Jianhai; Cheng, Pei Feng; Anderson, Sarah; Ulrich, Michelle; Hurley, James B; Raftery, Daniel; Ayer, Donald E; Eisenman, Robert N.
Afiliação
  • Carroll PA; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, MS A2-025, P.O. Box 19024, Seattle, WA 98109-1024, USA.
  • Diolaiti D; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, MS A2-025, P.O. Box 19024, Seattle, WA 98109-1024, USA.
  • McFerrin L; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, MS A2-025, P.O. Box 19024, Seattle, WA 98109-1024, USA.
  • Gu H; 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.
  • Djukovic D; 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.
  • Du J; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Cheng PF; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, MS A2-025, P.O. Box 19024, Seattle, WA 98109-1024, USA.
  • Anderson S; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, MS A2-025, P.O. Box 19024, Seattle, WA 98109-1024, USA.
  • Ulrich M; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, MS A2-025, P.O. Box 19024, Seattle, WA 98109-1024, USA.
  • Hurley JB; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Department of Ophthalmology, University of Washington, Seattle, WA 98195, USA.
  • Raftery D; 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, Seattl
  • Ayer DE; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA.
  • Eisenman RN; 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.
Cancer Cell ; 27(2): 271-85, 2015 Feb 09.
Article em En | MEDLINE | ID: mdl-25640402
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Proto-Oncogênicas c-myc / Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos / Neuroblastoma Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
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XML
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Proto-Oncogênicas c-myc / Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos / Neuroblastoma Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article