AUTHOR=Lee Jong-Ho , Shao Fei , Ling Jinjie , Lu Sean , Liu Rui , Du Linyong , Chung Jin Woong , Koh Sang Seok , Leem Sun-Hee , Shao Jichun , Xing Dongming , An Zhiqiang , Lu Zhimin 

TITLE=Phosphofructokinase 1 Platelet Isoform Promotes β-Catenin Transactivation for Tumor Development

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.00211

DOI=10.3389/fonc.2020.00211

ISSN=2234-943X

ABSTRACT=<p>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 <italic>CCND1</italic> and <italic>MYC</italic> 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.</p>