Abstract |
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.
|
Authors | 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 |
Journal | Frontiers in oncology
(Front Oncol)
Vol. 10
Pg. 211
( 2020)
ISSN: 2234-943X [Print] Switzerland |
PMID | 32195176
(Publication Type: Journal Article)
|
Copyright | Copyright © 2020 Lee, Shao, Ling, Lu, Liu, Du, Chung, Koh, Leem, Shao, Xing, An and Lu. |