Rauckhorst Adam J, Taylor Eric B
Department of Biochemistry, Fraternal Order of the Eagles Diabetes Research Center, Abboud Cardiovascular Research Center, Holden Comprehensive Cancer Center, and Pappajohn Biomedical Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Department of Biochemistry, Fraternal Order of the Eagles Diabetes Research Center, Abboud Cardiovascular Research Center, Holden Comprehensive Cancer Center, and Pappajohn Biomedical Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Curr Opin Genet Dev. 2016 Jun;38:102-109. doi: 10.1016/j.gde.2016.05.003. Epub 2016 Jun 5.
Metabolic reprogramming in cancer supports the increased biosynthesis required for unchecked proliferation. Increased glucose utilization is a defining feature of many cancers that is accompanied by altered pyruvate partitioning and mitochondrial metabolism. Cancer cells also require mitochondrial tricarboxylic acid cycle activity and electron transport chain function for biosynthetic competency and proliferation. Recent evidence demonstrates that mitochondrial pyruvate carrier (MPC) function is abnormal in some cancers and that increasing MPC activity may decrease cancer proliferation. Here we examine recent findings on MPC function and cancer metabolism. Special emphasis is placed on the compartmentalization of pyruvate metabolism and the alternative routes of metabolism that maintain the cellular biosynthetic pools required for unrestrained proliferation in cancer.
癌症中的代谢重编程支持了不受控制的增殖所需的生物合成增加。葡萄糖利用增加是许多癌症的一个决定性特征,同时伴随着丙酮酸分配和线粒体代谢的改变。癌细胞还需要线粒体三羧酸循环活性和电子传递链功能来实现生物合成能力和增殖。最近的证据表明,线粒体丙酮酸载体(MPC)功能在某些癌症中异常,增加MPC活性可能会降低癌症增殖。在这里,我们研究了关于MPC功能和癌症代谢的最新发现。特别强调了丙酮酸代谢的区室化以及维持癌症中不受限制的增殖所需的细胞生物合成池的替代代谢途径。