Deregulation of Glucose Transporter 1 and Glycolytic Gene Expression by c-Myc*

By Rebecca C. Osthus, Hyunsuk Shim, Sunkyu Kim, Qing Li, R. Reddy, Mita Mukherjee, Yi Xu, Diane R. Wonsey, Linda A. Lee, C. V. Dang. Journal of Biological Chemistry, 2000

879 citations recorded by the source corpus.

Unlike normal mammalian cells, which use oxygen to generate energy, cancer cells rely on glycolysis for energy and are therefore less dependent on oxygen. We previously observed that the c-Myc oncogenic transcription factor regulates lactate dehydrogenase A and induces lactate overproduction. We, therefore, sought to determine whether c-Myc controls other genes regulating glucose metabolism. In Rat1a fibroblasts and murine livers overexpressing c-Myc, the mRNA levels of the glucose transporter GLUT1, phosphoglucose isomerase, phosphofructokinase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and enolase were elevated. c-Myc directly transactivates genes encoding GLUT1, phosphofructokinase, and enolase and increases glucose uptake in Rat1 fibroblasts. Nuclear run-on studies confirmed that the GLUT1 transcriptional rate is elevated by c-Myc. Our findings suggest that overexpression of the c-Myc oncoprotein deregulates glycolysis through the activation of several components of the glucose metabolic pathway.

Subfields: Cancer Research, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/96e210ebe13277e413704d939c51488aebfab552

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Citations in the corpus

HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity. (2007, background): “Other transcription factors, including C-MYC (Shim et al., 1997; Osthus et al., 2000) and SP1/SP3 (Discher et al., 1998), contribute to the regulated expression of these genes.”
MYC on the Path to Cancer (2012, background): “In addition, Myc regulates energy metabolism through its direct activation of genes involved in glycolysis, glutamine metabolism, and mitochondrial biogenesis (Gao et al., 2009; Li et al., 2005; Osthus et al., 2000; Shim et al., 1997; Wise et al., 2008).”
The PI3K pathway in human disease (2017, positive): “, 2007) and c-Myc (Osthus et al., 2000), transcription factors that drive the expression of genes involved in glucose metabolism, including SLC2A1-encoding GLUT1.”
MYC, metabolism, cell growth, and tumorigenesis. (2013, neutral): “2) (Osthus et al. 2000; Hu et al. 2011).”
The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. (2008, background): “The transcription factor Myc (top right) increases expression of many metabolic enzymes, including glycolytic enzymes, LDH-A, and several enzymes required for nucleotide biosynthesis.”
Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase. (2001, methodology): “The self-contained tetracyline-repressor retroviral vector containing MyrAkt was constructed by introducing MyrAkt into the BamHI site of pBPSTR-1 (Paulus et al. 1996).”
MYC, Metabolism, and Cancer. (2015, background): “113, 114), loss of function of which diminishes cell proliferation and highlights their critical importance in cell growth (113, 115).”
Dietary Fiber Confers Protection against Flu by Shaping Ly6c− Patrolling Monocyte Hematopoiesis and CD8+ T Cell Metabolism (2018, background): “Extra- and intracellular levels of Glut-1 and c-myc, well-described inducers of glycolysis (Osthus et al., 2000; Palmer et al., 2015), were more potently increased upon stimulation of CD8+ T cells isolated from HFD-fed mice (Figure S6B).”
Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. (2011, positive): “In addition to promoting glutamine metabolism as discussed above, MYC promotes transcription of glucose transporters and glycolytic enzymes (Ahuja et al 2010, Osthus et al 2000).”
Akt Stimulates Aerobic Glycolysis in Cancer Cells (2004, background): “Other investigators have demonstrated the ability of c-Myc to promote glucose metabolism (30, 31), and c-Myc-transformed cells have also been demonstrated to be susceptible to”
Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer (2009, background): “Indeed, Myc increases expression of many metabolic and glycolytic enzymes, such as LDH-A as well as several enzymes required for nucleotides synthesis and ATP production [77, 78].”
HIF and c-Myc: sibling rivals for control of cancer cell metabolism and proliferation. (2007, background): “…independent of growth factor stimulation. c-Myc enhances the glycolytic pathway, increasing target gene expression from glucose transporters through pyruvate kinase (listed in Figure 1), as well as LDH-A, allowing efflux of glucose-derived carbon as lactate (Osthus et al., 2000; Shim et al., 1997).”
The Metabolic Profile of Tumors Depends on both the Responsible Genetic Lesion and Tissue Type (2012, background): “Some of the metabolic changes that are observed during MYC-induced tumorigenesis in both liver and lung, including increased expression of Hk2, Ldha, and Gls1, may be the result of MYC overexpression itself (Gao et al., 2009; Osthus et al., 2000; Wise et al., 2008).”
HIF‐1α induces cell cycle arrest by functionally counteracting Myc (2004, background): “Furthermore, Myc has also been shown to activate glucose transporter 1 and glycolytic genes (Osthus et al, 2000), transcriptional targets of HIF-1a as well.”