肿瘤细胞增殖依赖能量和物质代谢的支持。细胞周期不同阶段的代谢需求不同，细胞必须在代谢通路之间进行切换，这要求周期和代谢通路之间存在高效的交互调控，而目前对这类调控了解不多。我们前期的研究发现激酶Aurora-A在肿瘤细胞S和G2期通过改变LDHB的催化方向，促进糖酵解代谢中间物进入合成通路，从而保障S、G2期生物合成。我们还与合作者发现G2和M期，糖代谢支路磷酸戊糖途径激活，NADPH和R5P上升，但其功能和意义不清楚。我们近期利用活细胞代谢物探针技术，获得了NADPH在分裂期的动态特征，并发现增加的NADPH可以通过清除ROS避免染色体错误分离。本课题中我们将利用探针描绘redox相关代谢物在分裂期的变化规律，揭示NADPH代谢和调控机制，发现ROS的生成、转化和调控通路，阐明NADPH在染色体分离中的功能和对肿瘤增殖的意义，解析肿瘤细胞分裂调控信号和代谢通路之间交互协作的新机制。

Supplies of energy and building blocks are essential for cell cycle progression in tumors. As the demands varies over cell cycle phrases, the metabolic pathways should be rapidly switched accordingly. Modulations of metabolism by cell cycle regulators could be efficient strategies. However, how cells coordinate the cell cycle progression and metabolic pathways in mitosis is largely unknown. In a recent work, we found Aurora-A kinase promotes glycolysis and bio-synthesis by phosphorylation LDHB in S and G2 phrases. We and collaborators also found pentose phosphate pathway (PPP), a branch of glycolysis, is activated in G2/M phase, which was complied with recent finding that NADPH, a product of PPP, is elevated in mitosis. But the function of activated PPP in mitosis is unclear. Using metabolic biosensors, we validated that NADPH level fluctuates during mitosis and the up-regulated the pentose phosphate pathway accounts for high level of NADPH at early mitosis. Elimination of ROS with NADPH prevents chromosome mis-segregation. In this study, we will further analyze the temporal changes of redox related metabolites over mitotic progression and their dynamic regulation. We will also dissect the pathways that modulate PPP at G2/M transition, investigate the function of the regulation in various tumor cells and elucidate the mechanism behind dynamic modulation of metabolism over cell cycle progression.