中国科大揭示肿瘤细胞代谢重编程与周期调控新机制
中国科学技术大学生命学院张华凤课题组、高平课题组联合中科院合肥物质科学研究院强磁场科学中心王俊峰课题组,在肿瘤细胞的代谢重编程与周期调控研究领域取得进展,相关研究成果以Polo-like Kinase 1 Coordinates Biosynthesis during Cell Cycle Progression by Directly Activating Pentose Phosphate Pathway为题,近日在线发表在Nature Communications上。


本文转载自“中国科学技术大学”。

肿瘤代谢重编程和细胞周期调控异常是肿瘤的两个重要特征,然而人们尚不清楚这两者之间如何相互协调以促进肿瘤细胞的增殖和肿瘤的发生发展。课题组首次发现在肿瘤细胞中,重要的周期调控蛋白Plk1在周期进程中调节磷酸戊糖途径的关键代谢酶G6PD的活性,并进而促进生物大分子合成以及肿瘤细胞在体内外的增殖。

进一步的机制研究发现,Plk1通过结合并磷酸化修饰G6PD,使G6PD形成二聚体增多,从而促进酶活性以及整个磷酸戊糖途径。增强的磷酸戊糖途径对于肿瘤细胞的周期进程以及肿瘤的发生发展有重要的促进作用。该研究首次发现了周期调控蛋白Plk1在调节生物大分子合成方面的新功能,揭示了代谢重编程与周期调控相互协调共同促进肿瘤细胞快速增殖的新机制,对临床肿瘤的靶向治疗有潜在的指导意义。


中国科大揭示肿瘤细胞代谢重编程与周期调控新机制

研究工作在国家自然科学基金委、科技部以及中科院的资助下完成。

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  • Polo-like kinase 1 coordinates biosynthesis during cell cycle progression by directly activating pentose phosphate pathway

    Two hallmarks for cancer cells are the accelerated cell cycle progression as well as the altered metabolism, however, how these changes are coordinated to optimize the growth advantage for cancer cells are still poorly understood. Here we identify that Polo-like kinase 1 (Plk1), a key regulator for cell mitosis, plays a critical role for biosynthesis in cancer cells through activating pentose phosphate pathway (PPP). We find that Plk1 interacts with and directly phosphorylates glucose-6-phosphate dehydrogenase (G6PD). By activating G6PD through promoting the formation of its active dimer, Plk1 increases PPP flux and directs glucose to the synthesis of macromolecules. Importantly, we further demonstrate that Plk1-mediated activation of G6PD is critical for its role to promote cell cycle progression and cancer cell growth. Collectively, these findings establish a critical role for Plk1 in regulating biosynthesis in cancer cells, exemplifying how cell cycle progression and metabolic reprogramming are coordinated for cancer progression.

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