Cancer metabolism-key players in metabolic reprogramming英语教案.pdf

Review Article Cancer metabolism: Key players in metabolic reprogramming Tomoyoshi Soga1 Institute for Advanced Biosciences, Keio University, Tsuruoka, Japan (Received October 11, 2012⁄ Revised December 3, 2012⁄ Accepted December 10, 2012⁄ Accepted manuscript online December 20, 2012⁄ Article first published online January 31, 2013) Over 80 years ago, Warburg discovered that cancer cells generate cells.(7) This review covers the accumulated findings regarding ATP through the glycolytic pathway, even in the presence of oxy- key transcription factors and metabolic enzymes that induce gen. The finding of this phenomenon, termed the “Warburg alterations in cancer metabolism, which can be attractive tar- effect,” stimulated much research on tumorigenesis, but few gets for cancer therapy. explanations were forthcoming to explain the observation. Recently, advanced developments in molecular biology and high- The Warburg Effect throughput molecular analyses have revealed that many of the signaling pathways altered by gene mutations regulate cell One of the prominent characteristics of rapidly growing tumor metabolism in cancer. Furthermore, mutations in isocitrate dehy- cells is their capacity to sustain high rates of glycolysis for drogenase 1 and 2 were shown to elevate 2-hydroxyglutarate, ATP generation, irrespective of oxygen availability. This phe- which led to changes in a-ketoglutarate-dependent dioxygenase nomenon is known as the Warburg effect.(2,8,9) This character- enzyme activity, resulting in an increased risk of malignant istic seems to be a general property of highly malignant tumors. Although these findings led to a renewed interest in can-