Synthetic Essentiality of Metabolic Regulator PDHK1 in PTEN-Deficient Cells and Cancers | Zendy

Nilanjana Chatterjee | Zendy; Evangelos Pazarentzos | Zendy; Manasi K. Mayekar | Zendy; Philippe Gui | Zendy; David V. Allegakoen | Zendy; Gorjan Hrustanovic | Zendy; Victor Olivas | Zendy; Luping Lin | Zendy; Erik Verschueren | Zendy; Jeffrey R. Johnson | Zendy; Matan Hofree | Zendy; Jenny Yan | Zendy; Billy W. Newton | Zendy; John Von Dollen | Zendy; Charles H. Earnshaw | Zendy; Jennifer C. Flanagan | Zendy; Elton Chan | Zendy; Saurabh Asthana | Zendy; Trey Ideker | Zendy; Wei Wu | Zendy; Junji Suzuki | Zendy; Benjamin A. Barad | Zendy; Yuriy Kirichok | Zendy; James S. Fraser | Zendy; William A. Weiss | Zendy; Nevan J. Krogan | Zendy; Asmin Tulpule | Zendy; Amit J. Sabnis | Zendy; Trever G. Bivona | Zendy

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Synthetic Essentiality of Metabolic Regulator PDHK1 in PTEN-Deficient Cells and Cancers

Author(s) -

Nilanjana Chatterjee,

Evangelos Pazarentzos,

Manasi K. Mayekar,

Philippe Gui,

David V. Allegakoen,

Gorjan Hrustanovic,

Victor Olivas,

Luping Lin,

Erik Verschueren,

Jeffrey R. Johnson,

Matan Hofree,

Jenny Yan,

Billy W. Newton,

John Von Dollen,

Charles H. Earnshaw,

Jennifer C. Flanagan,

Elton Chan,

Saurabh Asthana,

Trey Ideker,

Wei Wu,

Junji Suzuki,

Benjamin A. Barad,

Yuriy Kirichok,

James S. Fraser,

William A. Weiss,

Nevan J. Krogan,

Asmin Tulpule,

Amit J. Sabnis,

Trever G. Bivona

Publication year - 2019

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2019.07.063

Subject(s) - pten , tensin , phosphatase , regulator , cancer research , biology , suppressor , tumor suppressor gene , gene , signal transduction , microbiology and biotechnology , phosphorylation , pi3k/akt/mtor pathway , biochemistry , carcinogenesis

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.

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