Phosphoglycerate Mutase Cooperates with Chk1 Kinase to Regulate Glycolysis
Phosphoglycerate Mutase Cooperates with Chk1 Kinase to Regulate Glycolysis
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DOI：
10.1016/j.isci.2020.101306
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发表时间：
2020-07-24
期刊：
影响因子：
5.8
通讯作者：
Kondoh, Hiroshi
中科院分区：
文献类型：
--
作者：
Mikawa, Takumi;Shibata, Eri;Kondoh, Hiroshi
糖酵解失调，包括癌性Warburg效应，与疾病状态的病理机制密切相关。在糖酵解酶中，已知磷酸甘油酸变异酶（PGAM）在体外发挥一定的生理作用，但其对糖酵解的调节作用尚不清楚。在这里，我们发现PGAM在调节癌细胞的糖酵解中起关键作用，但在标准细胞中不起作用。体内PGAM过表达的癌症易感表型与糖酵解特征上调相关。PGAM与Chk1相互作用并协同调节癌细胞中糖酵解的增强，特别是在致癌性Ras表达条件下。遗传或化学干扰的PGAM- chk1相互作用，与完整的PGAM活性，取消了维持癌增强糖酵解。因此，PGAM的非酶功能对于伴随癌性增殖的Warburg效应至关重要。
Dysregulated glycolysis, including the cancerous Warburg effect, is closely involved in pathological mechanisms of diseased states. Among glycolytic enzymes, phosphoglycerate mutase (PGAM) has been known to exert certain physiological impact in vitro, whereas its regulatory role on glycolysis remains un-clear. Here, we identified that PGAM plays a key role in regulating glycolysis in cancer cells but not in standard cells. Cancer-prone phenotype by PGAM overex-pression in vivo was associated with upregulated glycolytic features. PGAM inter-acts and cooperates with Chk1 to regulate the enhanced glycolysis in cancer cells, especially under oncogenic Ras expressing conditions. Genetic or chemical interference of the PGAM-Chk1 interaction, with intact PGAM activity, abro-gated the maintenance of cancerous enhanced glycolysis. Thus, the nonenzymatic function of PGAM is essential for the Warburg effect that accompanies cancerous proliferation.