Phosphofructokinase 1 Platelet Isoform Promotes β-Catenin Transactivation for Tumor Development
| Autor: | Jin Woong Chung, Jong Ho Lee, Fei Shao, Rui Liu, Sun Hee Leem, Dongming Xing, Linyong Du, Zhiqiang An, Sang Seok Koh, Zhimin Lu, Jinjie Ling, Jichun Shao, Sean Lu |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Gene isoform Cancer Research proliferation cyclin D1 migration lcsh:RC254-282 03 medical and health sciences Transactivation 0302 clinical medicine PFKP Gene expression Glycolysis Phosphofructokinase 1 Protein kinase B Original Research Chemistry β-catenin lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens invasion Cell biology 030104 developmental biology c-Myc Oncology 030220 oncology & carcinogenesis Phosphorylation |
| Zdroj: | Frontiers in Oncology Frontiers in Oncology, Vol 10 (2020) |
| ISSN: | 2234-943X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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