Stabilization of phosphofructokinase 1 platelet isoform by AKT promotes tumorigenesis

• DOI: 10.1038/s41467-017-00906-9
• Publication Date: 2017-10-10T17:39:46Z
• Authors: 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. de Groot; Tao Jiang; Zhimin Lu
• Keywords: 0303 health sciences; Brain Neoplasms; Carcinogenesis; Science; Q; PTEN Phosphohydrolase; Phosphofructokinase-1, Type C; Article; 03 medical and health sciences; Cell Line, Tumor; Humans; Phosphorylation; Glioblastoma; Glycolysis; Proto-Oncogene Proteins c-akt; Cell Proliferation

Phosphofructokinase 1 (PFK1) plays a critical role in glycolysis; however, its and regulation tumorigenesis are not well understood. Here, we demonstrate that PFK1 platelet isoform (PFKP) is the predominant human glioblastoma cells expression correlates with total PFK activity. We show PFKP overexpressed specimens due to an increased stability, which induced by AKT activation resulting from phosphatase tensin homologue (PTEN) loss EGFR-dependent PI3K activation. binds phosphorylates at S386, this phosphorylation inhibits binding of TRIM21 E3 ligase subsequent TRIM21-mediated polyubiquitylation degradation PFKP. S386 increases promotes aerobic glycolysis, cell proliferation, brain tumor growth. In addition, positively expression, S473 phosphorylation, poor prognosis. These findings underscore potential development.Phosphofructokinase glycolysis. Here authors upregulated Glioblastoma required for growth mechanistically, such upregulation stability via on residue S386.