Author/Authors :
Hatzivassiliou، نويسنده , , Georgia and Zhao، نويسنده , , Fangping and Bauer، نويسنده , , Daniel E. and Andreadis، نويسنده , , Charalambos and Shaw، نويسنده , , Anthony N. and Dhanak، نويسنده , , Dashyant and Hingorani، نويسنده , , Sunil R. and Tuveson، نويسنده , , David A. and Thompson، نويسنده , , Craig B.، نويسنده ,
Abstract :
Summary
umors display a high rate of glucose utilization, as evidenced by 18-F-2-deoxyglucose PET imaging. One potential advantage of catabolizing glucose through glycolysis at a rate that exceeds bioenergetic need is that the growing cell can redirect the excess glycolytic end product pyruvate toward lipid synthesis. Such de novo lipid synthesis is necessary for membrane production and lipid-based posttranslational modification of proteins. A key enzyme linking glucose metabolism to lipid synthesis is ATP citrate lyase (ACL), which catalyzes the conversion of citrate to cytosolic acetyl-CoA. ACL inhibition by RNAi or the chemical inhibitor SB-204990 limits in vitro proliferation and survival of tumor cells displaying aerobic glycolysis. The same treatments also reduce in vivo tumor growth and induce differentiation.
