MYC-induced Cancer Cell Energy Metabolism and Therapeutic Opportunities

By C. V. Dang, A. Le, Ping Gao. Clinical Cancer Research, 2009

895 citations recorded by the source corpus.

Although cancers have altered glucose metabolism, termed the Warburg effect, which describes the increased uptake and conversion of glucose to lactate by cancer cells under adequate oxygen tension, changes in the metabolism of glutamine and fatty acid have also been documented. The MYC oncogene, which contributes to the genesis of many human cancers, encodes a transcription factor c-Myc, which links altered cellular metabolism to tumorigenesis. c-Myc regulates genes involved in the biogenesis of ribosomes and mitochondria, and regulation of glucose and glutamine metabolism. With E2F1, c-Myc induces genes involved in nucleotide metabolism and DNA replication, and microRNAs that homeostatically attenuate E2F1 expression. With the hypoxia inducible transcription factor HIF-1, ectopic c-Myc cooperatively induces a transcriptional program for hypoxic adaptation. Myc regulates gene expression either directly, such as glycolytic genes including lactate dehydrogenase A (LDHA), or indirectly, such as repression of microRNAs miR-23a/b to increase glutaminase (GLS) protein expression and glutamine metabolism. Ectopic MYC expression in cancers, therefore, could concurrently drive aerobic glycolysis and/or oxidative phosphorylation to provide sufficient energy and anabolic substrates for cell growth and proliferation in the context of the tumor microenvironment. Collectively, these studies indicate that Myc-mediated altered cancer cell energy metabolism could be translated for the development of new anticancer therapies. (Clin Cancer Res 2009;15(21):6479–83)

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/7a83fc3cb08f937e3d158030c4115bcbaac10ec8

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Citations in the corpus

Obesity and Diabetes: The Increased Risk of Cancer and Cancer-Related Mortality. (2015, background): “Cells transformed by oncogenes, such as ras, src, and c-myc have been shown to activate GLUT1 and GLUT3 expression (40, 125).”
c-Myc and Cancer Metabolism (2012, neutral): “The c-Myc oncogene is overexpressed in the majority of human cancers and contributes to the cause of at least 40% of tumors (37).”
Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B-cells (2012, neutral): “Further, tumor suppressors such as p53 and oncogenes such as MYC and RAS have been directly linked to regulating metabolic pathways (Dang et al., 2009a; Telang et al., 2007) for initiating tumorigenesis and tumor progression.”
MYC activation is a hallmark of cancer initiation and maintenance. (2014, background): “These changes may make tumors particularly susceptible to the inhibition of enzymes that are essential for energy metabolism (Dang 1999, 2013; Dang et al. 2009; O’Shea and Ayer 2013).”
Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation (Review). (2012, background): “This process provides fuel for the passive TCA cycle due to a lack of isocitrate (2,7,39,46-48).”
BET bromodomain inhibition as a therapeutic strategy to target c-Myc (2011, neutral): “c-Myc is a master regulatory factor of cell proliferation (Dang et al., 2009).”
Cancer Cell Metabolism: One Hallmark, Many Faces (2012, background): “In several tumors however, Myc is a proto-oncogene that is aberrantly activated by gene amplification, single nucleotide polymorphisms, chromosomal translocations (53), or perhaps as a downstream consequence of mTORC1 hyperactivity.”
Metabolic Regulation of T Lymphocytes (2013, background): “Specifically, c-Myc can direct the expression of all the glycolytic genes, including Glut1, lactate dehydrogenase A (LDHA), PKM2, and hexokinase 2 (31), as well as glutaminase and the glutamine transporters SLC3a2, SLC5A1, and SLC7A1 (32, 33).”
Metabolic reprogramming: the emerging concept and associated therapeutic strategies (2015, background): “c-Myc promotes both glutamine uptake and glutamine catabolism [61].”
Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged. (2010, background): “The oncogenic transcription factor c-Myc is known to promote the up-regulation of LDH-A, as well as of several other glycolytic enzymes, an activity that appears to underlie, in part, the effect of Myc on aerobic glycolysis (Shim et al. 1997; Kim et al. 2004; Dang et al. 2009).”
Regulation of cancer cell metabolism (2011, background): “shtml?what=graphic&jpg=on&pathway_id=myc_pathway">MYC also has several important effects on cell metabolis”