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Stabilization of phosphofructokinase 1 platelet isoform by AKT promotes tumorigenesis

Author

Listed:
  • Jong-Ho Lee

    (The University of Texas MD Anderson Cancer Center)

  • Rui Liu

    (The University of Texas MD Anderson Cancer Center
    Sichuan University)

  • Jing Li

    (The University of Texas MD Anderson Cancer Center
    Sichuan University)

  • Chuanbao Zhang

    (Capital Medical University)

  • Yugang Wang

    (The University of Texas MD Anderson Cancer Center)

  • Qingsong Cai

    (The University of Texas MD Anderson Cancer Center)

  • Xu Qian

    (The University of Texas MD Anderson Cancer Center)

  • Yan Xia

    (The University of Texas MD Anderson Cancer Center)

  • Yanhua Zheng

    (The University of Texas MD Anderson Cancer Center)

  • Yuji Piao

    (The University of Texas MD Anderson Cancer Center)

  • Qianming Chen

    (Sichuan University)

  • John F. Groot

    (The University of Texas MD Anderson Cancer Center)

  • Tao Jiang

    (Capital Medical University)

  • Zhimin Lu

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center
    The University of Texas Graduate School of Biomedical Sciences at Houston)

Abstract

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.

Suggested Citation

  • Jong-Ho Lee & Rui Liu & Jing Li & Chuanbao Zhang & Yugang Wang & Qingsong Cai & Xu Qian & Yan Xia & Yanhua Zheng & Yuji Piao & Qianming Chen & John F. Groot & Tao Jiang & Zhimin Lu, 2017. "Stabilization of phosphofructokinase 1 platelet isoform by AKT promotes tumorigenesis," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00906-9
    DOI: 10.1038/s41467-017-00906-9
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    Cited by:

    1. Eric M. Lynch & Heather Hansen & Lauren Salay & Madison Cooper & Stepan Timr & Justin M. Kollman & Bradley A. Webb, 2024. "Structural basis for allosteric regulation of human phosphofructokinase-1," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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