Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China.
High Magnetic Field Laboratory, Chinese Academy of Sciences, 350 Shushanhu Road, Hefei, Anhui, 230031, China.
Nat Commun. 2017 Nov 15;8(1):1506. doi: 10.1038/s41467-017-01647-5.
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.
癌细胞的两个特征是细胞周期的加速进展和代谢的改变，然而，这些变化如何协调以优化癌细胞的生长优势仍知之甚少。在这里，我们发现细胞有丝分裂的关键调节因子 Polo 样激酶 1（Plk1）通过激活戊糖磷酸途径（PPP）在癌细胞的生物合成中起着关键作用。我们发现 Plk1 与葡萄糖-6-磷酸脱氢酶（G6PD）相互作用，并直接磷酸化 G6PD。通过促进其活性二聚体的形成来激活 G6PD，Plk1 增加 PPP 通量并将葡萄糖引导至大分子的合成。重要的是，我们进一步证明 Plk1 介导的 G6PD 激活对于促进细胞周期进程和癌细胞生长的作用至关重要。总的来说，这些发现确立了 Plk1 在调节癌细胞生物合成中的关键作用，说明了细胞周期进程和代谢重编程如何协调促进癌症进展。
