Image_1_Phosphofructokinase 1 Platelet Isoform Promotes β-Catenin Transactivation for Tumor Development.tif (1.55 MB)

Image_1_Phosphofructokinase 1 Platelet Isoform Promotes β-Catenin Transactivation for Tumor Development.tif

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posted on 05.03.2020, 04:13 by Jong-Ho Lee, Fei Shao, Jinjie Ling, Sean Lu, Rui Liu, Linyong Du, Jin Woong Chung, Sang Seok Koh, Sun-Hee Leem, Jichun Shao, Dongming Xing, Zhiqiang An, Zhimin Lu

Metabolism plays a critical role in direct regulation of a variety of cellular activities via metabolic enzymes and metabolites. Here, we demonstrate that phosphofructokinase 1 platelet isoform (PFKP), which catalyzes a rate-limiting reaction in glycolysis, promotes EGFR activation-induced nuclear translocation and activation of β-catenin, thereby enhancing the expression of its downstream genes CCND1 and MYC in human glioblastoma cells. Importantly, we showed that EGFR-phosphorylated PFKP Y64 has a critical role in AKT activation and AKT-mediated β-catenin S552 phosphorylation and subsequent β-catenin transactivation and promotion of tumor cell glycolysis, migration, invasion, proliferation, and brain tumor growth. These findings highlight a novel mechanism underlying a glycolytic enzyme-mediated β-catenin transactivation and underscore the integrated and reciprocal regulation of metabolism and gene expression, which are two fundamental biological processes in tumor development.

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