ArticleCell reports2019
Synthetic Essentiality of Metabolic Regulator PDHK1 in PTEN-Deficient Cells and Cancers.
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Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Article
- Living Biotherapeutics Using Nanoparticles-Armed Cyanobacteria for Boosting Photodynamic-Immunotherapy of Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- SNHG12 downregulation induces follicular dysplasia by modulating the glycolysis of granulosa cell in polycystic ovary syndrome.Frontiers in cell and developmental biology · 2025Article
- Synthetic lethal approaches to target cancers with loss of PTEN function.Genes & diseases · 2023Article
- YY1 transcription factor induces proliferation and aerobic glycolysis of neuroblastoma cells via LDHA regulation.Experimental and therapeutic medicine · 2023Article
- Synthetic essentiality between PTEN and core dependency factor PAX7 dictates rhabdomyosarcoma identity.Nature communications · 2021Article
- Organelle Crosstalk Regulators Are Regulated in Diseases, Tumors, and Regulatory T Cells: Novel Classification of Organelle Crosstalk Regulators.Frontiers in cardiovascular medicine · 2021Article
- MARCKS cooperates with NKAP to activate NF-kB signaling in smoke-related lung cancer.Theranostics · 2021Article
- Recent advances in PTEN signalling axes in cancer.Faculty reviews · 2020Review
- The Mechanisms Underlying PTEN Loss in Human Tumors Suggest Potential Therapeutic Opportunities.Biomolecules · 2019Review
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Authors and funding
29 authors.
Nilanjana ChatterjeeDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: nilanjana.chatterjee@ucsf.edu.
Evangelos PazarentzosDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Manasi K MayekarDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Philippe GuiDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
David V AllegakoenDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Gorjan HrustanovicDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Victor OlivasDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Luping LinDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Erik VerschuerenJ. David Gladstone Institutes, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; QB3, California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA.
Jeffrey R JohnsonJ. David Gladstone Institutes, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; QB3, California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA.
Matan HofreeDepartment of Bioengineering, University of California, San Diego, San Diego, CA 92093, USA.
Jenny J YanDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Billy W NewtonJ. David Gladstone Institutes, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; QB3, California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA.
John V DollenJ. David Gladstone Institutes, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; QB3, California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA.
Charles H EarnshawDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Jennifer FlanaganDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Elton ChanDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Saurabh AsthanaHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Trey IdekerDepartment of Bioengineering, University of California, San Diego, San Diego, CA 92093, USA.
Wei WuDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Junji SuzukiDepartment of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.
Benjamin A BaradDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA.
Yuriy KirichokDepartment of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.
James S FraserDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA.
William A WeissDepartment of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA.
Nevan J KroganJ. David Gladstone Institutes, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; QB3, California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA.
Asmin TulpuleHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Amit J SabnisHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Trever G BivonaDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; QB3, California Institute for Quantitative Biosciences, San Francisco, CA 94158, USA. Electronic address: trever.bivona@ucsf.edu.
Funding
UCSF Project 1U54CA224081 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Trever G Bivona, Jack Roth · 2017 to 2026
$12.9MUsing Networks to Seed Hierarchical Whole-cell Models of CancerU54CA209891 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ASHWORTH, ALAN · 2017 to 2021
$10.9MMolecular and Cellular Mechanisms in CancerT32CA108462 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GOGA, ANDREI · 2004 to 2024
$10.4MSTRUCTURAL BIOLOGY TRAINING PROGRAMT32GM008284 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KORTEMME, TANJA · 1988 to 2022
$10.1MResearch Training in Childhood CancerT32CA128583 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Eric Alejandro Sweet-Cordero · 2007 to 2026
$6.0MThe Cancer Target Discovery and Development Network at UCSFU01CA217882 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BANDYOPADHYAY, SOURAV, BIVONA, TREVER G · 2017 to 2021
$5.2MMolecular Biophysics of Mitochondrial MembranesR35GM136415 · NIGMS · WASHINGTON UNIVERSITY · PI Yuriy Kirichok · 2020 to 2026
$4.7MCharacterization of YAP as a rational companion target in lung cancerR01CA204302 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Trever G Bivona · 2017 to 2026
$3.7MRational Combined Inhibition of NF-kB and EGFR to Optimize Lung Cancer TreatmentR01CA169338 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BIVONA, TREVER G · 2013 to 2023
$3.4MDiscovery of Rational Companion Therapeutic Targets to Optimize Cancer TreatmentDP2CA174497 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BIVONA, TREVER G · 2012 to 2012
$2.3MSupplement to Resolving ensemble averaged conformations by multi-temperature x-ray crystallography - Equipment 2020R01GM123159 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FRASER, JAMES SOLOMON · 2018 to 2021
$2.3MMolecular Mechanisms of Mitochondrial Uncoupling and ThermogenesisR01GM118939 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KIRICHOK, YURIY · 2017 to 2020
$1.8MNCI NIH HHS DP2 CA174497NCI NIH HHS K08 CA218691NCI NIH HHS R01 CA169338NCI NIH HHS R01 CA204302NCI NIH HHS R01 CA211052NCI NIH HHS T32 CA108462NCI NIH HHS T32 CA128583NCI NIH HHS U01 CA217882NCI NIH HHS U54 CA209891NCI NIH HHS U54 CA224081NIGMS NIH HHS R01 GM118939NIGMS NIH HHS R01 GM123159NIGMS NIH HHS R35 GM136415NIGMS NIH HHS T32 GM008284
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.
Indexed as
AnimalsCell Line, TumorFemaleGlycolysisHEK293 CellsHumansMaleMiceMice, Inbred NODMice, SCIDNeoplasmsNF-kappa BPTEN PhosphohydrolasePyruvate Dehydrogenase Acetyl-Transferring KinaseRepressor ProteinsNF-kappa BNKAP protein, humanPDK1 protein, humanPTEN PhosphohydrolasePyruvate Dehydrogenase Acetyl-Transferring KinaseRepressor ProteinscancermetabolismNF-κBNKAPPDHK1protein phosphatasePTENsignalingsynthetic lethality
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.