| Literature DB >> 31461649 |
Nilanjana Chatterjee1, Evangelos Pazarentzos2, Manasi K Mayekar2, Philippe Gui2, David V Allegakoen2, Gorjan Hrustanovic2, Victor Olivas2, Luping Lin2, Erik Verschueren3, Jeffrey R Johnson3, Matan Hofree4, Jenny J Yan2, Billy W Newton3, John V Dollen3, Charles H Earnshaw5, Jennifer Flanagan2, Elton Chan2, Saurabh Asthana6, Trey Ideker4, Wei Wu2, Junji Suzuki7, Benjamin A Barad8, Yuriy Kirichok7, James S Fraser8, William A Weiss9, Nevan J Krogan3, Asmin Tulpule6, Amit J Sabnis6, Trever G Bivona10.
Abstract
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor and bi-functional lipid and protein phosphatase. We report that the metabolic regulator pyruvate dehydrogenase kinase1 (PDHK1) is a synthetic-essential gene in PTEN-deficient cancer and normal cells. The PTEN protein phosphatase dephosphorylates nuclear factor κB (NF-κB)-activating protein (NKAP) and limits NFκB activation to suppress expression of PDHK1, a NF-κB target gene. Loss of the PTEN protein phosphatase upregulates PDHK1 to induce aerobic glycolysis and PDHK1 cellular dependence. PTEN-deficient human tumors harbor increased PDHK1, a biomarker of decreased patient survival. This study uncovers a PTEN-regulated signaling pathway and reveals PDHK1 as a potential target in PTEN-deficient cancers.Entities:
Keywords: NF-κB; NKAP; PDHK1; PTEN; cancer; metabolism; protein phosphatase; signaling; synthetic lethality
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Year: 2019 PMID： 31461649 PMCID： PMC6728083 DOI： 10.1016/j.celrep.2019.07.063
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423