Melanoma Molecular Maps Projects



Title: Glucose metabolism in cancer (Warburg effect)
Legend: Malignant (including melanoma) cells rely on glycolysis for energy production more than normal cells, even in the presence of oxygen [4,6]: this phenomenon, called Warburg effect [1] or aerobic glycolysis, is accompanied with increased glucose uptake (the basis for Positron Emission Tomography [PET] scan), excessive lactate production leading to acidosis (which promotes cancer/melanoma aggressiveness [2,3]) and overexpression of glycolysis-related enzymes (e.g. LDH, a commonly used serum marker in metastatic melanoma), which often correlates with poor patients' prognosis. The reasons for this altered metabolism are only beginning to be elucidated: besides a generic glucose avidity proper of all proliferating cells (both normal and malignant), defects in mitochondrial functioning are believed to play a key role [5], which would also explain cancer cell resistance to apoptosis (which is mediated in large part by mitochondria). REFERENCES: [1] Warburg O, Science 1956, 124:269-70. [2] Martinez-Zaguilan R, Clin Exp Metastasis 1996, 14:176-86. [3] Fang JS, Semin Cancer Biol 2008, 18:330-7. [4] Ortega AD, Cancer Lett 2008, Epub ahead of print. [5] Lopez-Rios F, Cancer Res 2007, 67:9013-7. [6] Kroemer G, Cancer Cell 2008, 13:472-82. CITED MOLECULES: Acetyl-CoA, AKT (PKB), Aldolase, Alpha-ketoglutarate, Asp (aspartate), ATPS (ATP synthase), CD147 (basigin), Citrate, c-MYC (v-Myc myelocytomatosis viral oncogene homolog), Cyclin D1, Cys (cysteine), CYTCOX (cytochrome c oxidase), Delta-aminolevulinate, Exokinase, GADPH (glyceraldehyde 3-phosphate dehydrogenase) , Gln (glutamine), GlnS (glutamine synthetase), Glu (glutamate), Glucose-1P, Glucose-6P, GLUT1, (glucose transporter 1), Gly (glycine), HIF1-alpha (hypoxia-inducible factor 1, alpha subunit), Lactate, LDH (lactate dehydrogenase), MCT (Monocarboxylate transporter), Mevalonate, NAD+ (nicotinamide adenine dinucleotide), NADH, (NAD reduced form), NH3 (ammonia), Oxaloacetate, p53, PDH (pyruvate dehydrogenase), PDHK (PDH kinase), PFK (phosphofructokinase), PGK (phosphoglycerate kinase), PGM (phosphoglucomutase), Phe (phenylalanine), PPP (pentose phosphate pathway), PK (pyruvate kinase), Proteasome, Pyruvate, SCO2 (SCO cytochrome oxidase deficient homolog 2), Ser (serine), Succinil-CoA, TIGAR (C12orf5, TP53-induced glycolysis and apoptosis regulator), TCA Cycle (tricarboxylic acid cycle), Trp (tryptophan), Tyr (tyrosine). Figure #78
Author: The MMMP Team (updated: September 2008)

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