MYC and metabolism on the path to cancer

Article ID	Journal	Published Year	Pages	File Type
8480349	Seminars in Cell & Developmental Biology	2015	41 Pages	PDF

Abstract

The MYC proto-oncogene is frequently deregulated in human cancers, activating genetic programs that orchestrate biological processes to promote growth and proliferation. Altered metabolism characterized by heightened nutrients uptake, enhanced glycolysis and glutaminolysis and elevated fatty acid and nucleotide synthesis is the hallmark of MYC-driven cancer. Recent evidence strongly suggests that Myc-dependent metabolic reprogramming is critical for tumorigenesis, which could be attenuated by targeting specific metabolic pathways using small drug-like molecules. Understanding the complexity of MYC-mediated metabolic re-wiring in cancers as well as how MYC cooperates with other metabolic drivers such as mammalian target of rapamycin (mTOR) will provide translational opportunities for cancer therapy.

Keywords

AMPK PI3K ACC DOX GTP THF mRNA MYC SCD flavin adenine dinucleotide NADPH ChIP-Seq GAPDH SAM mTOR G3P GDH SHMT GPT HMGCR 5-Methyltetrahydrofolate GLS MPA GSK3 stearoyl-CoA desaturase NAMPT SAH GLUT hnRNP 2-Deoxyglucose PKM eIF4E MAX mTORC1 MITF RPS RPL 4E-BP inosine monophosphate dehydrogenase PDK1 ChREBP SREBP S-adenosylhomocysteine ACLY HIF1α MGA TFEB Cryptochrome R5P PFK Hmg tRNA αKG MNT mTORC2 TFE3 TSC2 MTHF ATP-citrate lyase PHGDH PSAT1 mTOR complex 2 PSPH MIZ1 PRPP MXI1 MXD rRNA FADH Myc associated factor X Transcription factor E3 PRPS1 RNA polymerase II 2-DG 5,10-Methylenetetrahydrofolate AMP-activated protein kinase HMG-CoA reductase mTOR complex 1 PI(3,4,5)P3 PI(4,5)P2 messenger RNA Ribosomal RNA RNA polymerase I RNA polymerase III ROS S-adenosyl-L-homocysteine hydrolase α-ketoglutarate Fatty acid β-oxidation Adenosine Triphosphate ATP acetyl-CoA carboxylase fatty acid synthase transfer RNA GOT tetrahydrofolate chromatin immunoprecipitation sequencing forkhead Box O Glucose transporter doxycycline per Period ribose 5-phosphate Heterogeneous nuclear ribonucleoproteins Small ribosomal subunit large ribosomal subunit Cancer serine hydroxymethyltransferase thymidylate synthase SAHH eukaryotic initiation factor 4E Transcription factor EB FAO Microphthalmia-associated transcription factor FoxO Fasn phosphatidylinositol-4,5-bisphosphate Phosphoserine phosphatase phosphoglycerate dehydrogenase Phosphofructokinase phosphoinositide 3-kinase lactate dehydrogenase LDH mycophenolic acid Metabolism NADH nicotinamide adenine dinucleotide nicotinamide adenine dinucleotide phosphate nicotinamide phosphoribosyltransferase mammalian target of rapamycin pleckstrin-homology eIF4E-binding protein carbohydrate response element binding protein Sterol regulatory element-binding protein Pol III Pol II Pol I pyruvate kinase tuberous sclerosis complex 2 TCA cycle tricarboxylic acid cycle phosphoinositide-dependent kinase Cry Glutaminase glyceraldehyde 3-phosphate dehydrogenase glycogen synthase kinase 3 Reactive oxygen species