机构：[1]Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.[2]State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.[3]Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China.首都医科大学附属天坛医院[4]Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.[5]The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA.
Phosphofructokinase 1 (PFK1) plays a critical role in glycolysis; however, its role and regulation in tumorigenesis are not well understood. Here, we demonstrate that PFK1 platelet isoform (PFKP) is the predominant PFK1 isoform in human glioblastoma cells and its expression correlates with total PFK activity. We show that PFKP is overexpressed in human glioblastoma specimens due to an increased stability, which is induced by AKT activation resulting from phosphatase and tensin homologue (PTEN) loss and EGFR-dependent PI3K activation. AKT binds to and phosphorylates PFKP at S386, and this phosphorylation inhibits the binding of TRIM21 E3 ligase to PFKP and the subsequent TRIM21-mediated polyubiquitylation and degradation of PFKP. PFKP S386 phosphorylation increases PFKP expression and promotes aerobic glycolysis, cell proliferation, and brain tumor growth. In addition, S386 phosphorylation in human glioblastoma specimens positively correlates with PFKP expression, AKT S473 phosphorylation, and poor prognosis. These findings underscore the potential role and regulation of PFKP in human glioblastoma development.Phosphofructokinase 1 (PFK1) plays a critical role in glycolysis. Here the authors show that PFK1 platelet isoform is upregulated in Glioblastoma and is required for tumor growth mechanistically, such upregulation is due to an increased stability induced by AKT activation via phosphorylation on residue S386.
基金：
This work was supported by National Institute of Neurological
Disorders and Stroke grant 1R01 NS089754 (Z.L.), National Cancer Institute grants 2R01
CA109035 (Z.L.) and 1R0 CA169603 (Z.L.), MD Anderson Support Grant CA016672,
the James S. McDonnell Foundation 21st Century Science Initiative in Brain Cancer
Research Award 220020318 (Z.L.), 2P50 CA127001 (Brain Cancer SPORE), and a Sister
Institution Network Fund from MD Anderson (Z.L.). Z.L. is a Ruby E. Rutherford
Distinguished Professor.
第一作者机构：[1]Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
通讯作者：
通讯机构：[1]Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.[4]Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.[5]The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA.
推荐引用方式(GB/T 7714)：
Jong-Ho Lee,Rui Liu,Jing Li,et al.Stabilization of phosphofructokinase 1 platelet isoform by AKT promotes tumorigenesis.[J].NATURE COMMUNICATIONS.2017,8:doi:10.1038/s41467-017-00906-9.
APA：
Jong-Ho Lee,Rui Liu,Jing Li,Chuanbao Zhang,Yugang Wang...&Zhimin Lu.(2017).Stabilization of phosphofructokinase 1 platelet isoform by AKT promotes tumorigenesis..NATURE COMMUNICATIONS,8,
MLA：
Jong-Ho Lee,et al."Stabilization of phosphofructokinase 1 platelet isoform by AKT promotes tumorigenesis.".NATURE COMMUNICATIONS 8.(2017)
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