Sugar and fat - that's where it's at: metabolic changes in tumors.
Tumor cells exhibit an altered metabolism, characterized by increased glucose uptake and elevated glycolysis, which was first recognized by Otto Warburg 70 years ago. Warburg originally hypothesized that these metabolic changes reflected damage to mitochondrial oxidative phosphorylation. Although hypoxia and hypoxia inducible factor can induce transcriptional changes that stimulate glucose transport and glycolysis, it is clear that these changes can occur in cultured tumor or transformed cells cultured under normoxic conditions, and thus there must be genetic alterations independent of hypoxia that can stimulate aerobic glycolysis. In recent years it has become clear that loss of p53 and activation of Akt can induce all or part of the metabolic changes reflected in the Warburg effect. Likewise, changes in expression of lactate dehydrogenase and other glycolytic control enzymes can contribute to increased or altered glycolysis. It is also clear that changes in lipid biosynthesis occur in tumor cells to support increased membrane biosynthesis and perhaps the altered energy needs of the cells. Changes in fatty acid synthase, Spot 14, Akt, and DecR1 (2,4-dienoylcoenzyme A reductase) may underlie altered lipid metabolism in tumor cells and contribute to the ability of tumor cells to proliferate or metastasize. Although these advances provide new therapeutic targets that merit exploration, there remain critical questions to be explored at the mechanistic level; this work may yield insights into tumor cell biology and identify additional therapeutic targets.
Young
Christian D
CD
Department of Pathology and Program in Cancer Biology, University of Colorado Denver, Anschutz Medical Campus, East 17th Avenue, Aurora, Colorado 80045, USA.
Anderson
Steven M
SM
D001943:Breast Neoplasms / Q000378:metabolism*; D005223:Fats / Q000378:metabolism*; D005260:Female; D016158:Genes, p53 / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D050356:Lipid Metabolism; D008928:Mitochondria / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism; D010085:Oxidative Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D005223:Fats; D009687:Nuclear Proteins; C051065:THRSP protein, human; D014157:Transcription Factors; D007770:L-Lactate Dehydrogenase; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose