Polo-like kinase 4 promotes tumorigenesis and glucose metabolism in glioma by activating AKT1 signaling

Glioblastoma (GBM) is an extremely aggressive tumor associated with a poor prognosis that impacts the central nervous system. Increasing evidence suggests an inherent association between glucose metabolism dysregulation and the aggression of GBM. Polo-like kinase 4 (PLK4), a highly conserved serine/...

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Bibliographic Details
Published in:Cancer letters 2024-03, Vol.585, p.216665-216665, Article 216665
Main Authors: Wang, Bo, Zhang, Xiaoyang, Li, Ze-sheng, Wei, Cheng, Yu, Run-ze, Du, Xue-zhi, He, Ying-jie, Ren, Yu, Zhen, Ying-wei, Han, Lei
Format: Article
Language:English
Subjects:
AKT1
Glioma
Kinase
Metabolism
PLK4
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Summary:Glioblastoma (GBM) is an extremely aggressive tumor associated with a poor prognosis that impacts the central nervous system. Increasing evidence suggests an inherent association between glucose metabolism dysregulation and the aggression of GBM. Polo-like kinase 4 (PLK4), a highly conserved serine/threonine protein kinase, was found to relate to glioma progression and unfavorable prognosis. As revealed by the integration of proteomics and phosphoproteomics, PLK4 was found to be involved in governing metabolic processes and the PI3K/AKT/mTOR pathway. For the first time, this study supports evidence demonstrating that PLK4 activated PI3K/AKT/mTOR signaling through direct binding to AKT1 and subsequent phosphorylating AKT1 at S124, T308, and S473 to promote tumorigenesis and glucose metabolism in glioma. In addition, PLK4-mediated phosphorylation of AKT1 S124 significantly augmented the phosphorylation of AKT1 S473. Therefore, PLK4 exerted an influence on glucose metabolism by stimulating PI3K/AKT/mTOR signaling. Additionally, the expression of PLK4 protein exhibited a positive correlation with AKT1 phosphorylation in glioma patient tissues. These findings highlight the pivotal role of PLK4-mediated phosphorylation of AKT1 in glioma tumorigenesis and dysregulation of glucose metabolism. •This study unveiled a novel role of PLK4 in glioma, wherein it exerted regulatory control over glucose metabolism.•AKT1 was identified as a novel substrate for PLK4, and PLK4 could phosphorylate AKT1 at three distinct sites.•A novel function of AKT1 S124 had been identified to facilitate the AKT1 S473 phosphorylation.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2024.216665