[PDF][PDF] ATP citrate lyase inhibition can suppress tumor cell growth
G Hatzivassiliou, F Zhao, DE Bauer, C Andreadis… - Cancer cell, 2005 - cell.com
G Hatzivassiliou, F Zhao, DE Bauer, C Andreadis, AN Shaw, D Dhanak, SR Hingorani…
Cancer cell, 2005•cell.comMany tumors 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 …
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 …
Summary
Many tumors 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.
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