{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Liang J"],"funding":["NCI NIH HHS","NINDS NIH HHS"],"pagination":["12431"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4976202"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7"],"pubmed_abstract":["Many types of human tumour cells overexpress the dual-specificity phosphatase Cdc25A. Cdc25A dephosphorylates cyclin-dependent kinase and regulates the cell cycle, but other substrates of Cdc25A and their relevant cellular functions have yet to be identified. We demonstrate here that EGFR activation results in c-Src-mediated Cdc25A phosphorylation at Y59, which interacts with nuclear pyruvate kinase M2 (PKM2). Cdc25A dephosphorylates PKM2 at S37, and promotes PKM2-dependent β-catenin transactivation and c-Myc-upregulated expression of the glycolytic genes GLUT1, PKM2 and LDHA, and of CDC25A; thus, Cdc25A upregulates itself in a positive feedback loop. Cdc25A-mediated PKM2 dephosphorylation promotes the Warburg effect, cell proliferation and brain tumorigenesis. In addition, we identify pos"],"journal":["Nature communications"],"pubmed_title":["PKM2 dephosphorylation by Cdc25A promotes the Warburg effect and tumorigenesis."],"pmcid":["PMC4976202"],"funding_grant_id":["R01 CA204996","P30 CA016672","R01 CA109035","R01 NS089754","R01 CA169603"],"pubmed_authors":["Xia Y","Li X","Yang W","Zheng Y","Zhang Y","Liang J","Lu Z","Cao R","Wang L"],"additional_accession":[]},"is_claimable":false,"name":"PKM2 dephosphorylation by Cdc25A promotes the Warburg effect and tumorigenesis.","description":"Many types of human tumour cells overexpress the dual-specificity phosphatase Cdc25A. Cdc25A dephosphorylates cyclin-dependent kinase and regulates the cell cycle, but other substrates of Cdc25A and their relevant cellular functions have yet to be identified. We demonstrate here that EGFR activation results in c-Src-mediated Cdc25A phosphorylation at Y59, which interacts with nuclear pyruvate kinase M2 (PKM2). Cdc25A dephosphorylates PKM2 at S37, and promotes PKM2-dependent β-catenin transactivation and c-Myc-upregulated expression of the glycolytic genes GLUT1, PKM2 and LDHA, and of CDC25A; thus, Cdc25A upregulates itself in a positive feedback loop. Cdc25A-mediated PKM2 dephosphorylation promotes the Warburg effect, cell proliferation and brain tumorigenesis. In addition, we identify pos","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Aug","modification":"2026-05-05T16:04:23.656Z","creation":"2019-03-27T02:20:06Z"},"accession":"S-EPMC4976202","cross_references":{"pubmed":["27485204"],"doi":["10.1038/ncomms12431"]}}