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

Animals Cell Line, Tumor Female Glycolysis HEK293 Cells Humans Male Mice Mice, Inbred NOD Mice, SCID NF-kappa B / metabolism Neoplasms / genetics PTEN Phosphohydrolase / economics Pyruvate Dehydrogenase Acetyl-Transferring Kinase / genetics Repressor Proteins / metabolism
NF-κB NKAP PDHK1 PTEN cancer metabolism protein phosphatase signaling synthetic lethality

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
27 08 2019
Historique:
received: 22 10 2018
revised: 19 06 2019
accepted: 18 07 2019
entrez: 29 8 2019
pubmed: 29 8 2019
medline: 26 8 2020
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.celrep.2019.07.063 PMID: 31461649 PMC: PMC6728083
pubmed: 31461649
pii: S2211-1247(19)30967-2
doi: 10.1016/j.celrep.2019.07.063
pmc: PMC6728083
mid: NIHMS1538444
pii:
doi:

Substances chimiques

NF-kappa B 0
NKAP protein, human 0
PDK1 protein, human 0
Pyruvate Dehydrogenase Acetyl-Transferring Kinase 0
Repressor Proteins 0
PTEN Phosphohydrolase EC 3.1.3.67

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2317-2330.e8

Subventions

Organisme : NCI NIH HHS
ID : U01 CA217882
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008284
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA224081
Pays : United States
Organisme : NCI NIH HHS
ID : DP2 CA174497
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM136415
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA209891
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA169338
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA218691
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA128583
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA204302
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM118939
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA211052
Pays : United States

Informations de copyright

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

Références

Trends Cell Biol. 1999 Apr;9(4):125-8
pubmed: 10203785
Proc Natl Acad Sci U S A. 1999 May 25;96(11):6199-204
pubmed: 10339565
Nature. 1999 Jun 10;399(6736):597-601
pubmed: 10376602
Bioinformatics. 1999 Jul-Aug;15(7-8):622-30
pubmed: 10487870
Cell. 1999 Oct 29;99(3):323-34
pubmed: 10555148
Exp Cell Res. 2000 May 1;256(2):571-7
pubmed: 10772829
Tanpakushitsu Kakusan Koso. 2000 Oct;45(14):2405-14
pubmed: 11051842
J Biol Chem. 2001 Feb 23;276(8):5731-8
pubmed: 11092882
Cancer Res. 2000 Dec 15;60(24):7075-83
pubmed: 11156414
J Biol Chem. 2001 Apr 6;276(14):11402-8
pubmed: 11278366
J Biol Chem. 2001 Jul 20;276(29):27740-4
pubmed: 11356844
Genes Dev. 2001 Jun 1;15(11):1406-18
pubmed: 11390360
Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10314-9
pubmed: 11504908
J Biol Chem. 2002 Mar 29;277(13):11116-25
pubmed: 11799112
Clin Cancer Res. 2002 May;8(5):1178-84
pubmed: 12006535
Cancer Cell. 2003 Feb;3(2):117-30
pubmed: 12620407
Science. 1956 Feb 24;123(3191):309-14
pubmed: 13298683
Arch Biochem Biophys. 1958 Dec;78(2):587-97
pubmed: 13618041
Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12247-52
pubmed: 14527995
Biochem Biophys Res Commun. 2003 Oct 24;310(3):720-4
pubmed: 14550261
Methods Enzymol. 2003;366:43-56
pubmed: 14674238
Oncogene. 2004 Sep 2;23(40):6788-97
pubmed: 15273733
EMBO J. 2006 Feb 22;25(4):910-20
pubmed: 16456542
Cell Metab. 2006 Mar;3(3):177-85
pubmed: 16517405
Oncogene. 2006 Oct 30;25(51):6680-4
pubmed: 17072321
Cell. 2007 Jan 12;128(1):157-70
pubmed: 17218262
Cancer Cell. 2007 Jan;11(1):37-51
pubmed: 17222789
Curr Biol. 2007 Jan 23;17(2):115-25
pubmed: 17240336
Structure. 2007 Aug;15(8):992-1004
pubmed: 17683942
Urol J. 2007 Spring;4(2):95-100
pubmed: 17701929
Exp Hematol. 2007 Oct;35(10):1495-509
pubmed: 17889719
J Cell Sci. 2008 Feb 1;121(Pt 3):249-53
pubmed: 18216329
Cancer Res. 2008 Mar 15;68(6):1862-71
pubmed: 18339867
Genes Dev. 2008 Jun 1;22(11):1490-500
pubmed: 18519641
J Med Chem. 2008 Sep 25;51(18):5522-32
pubmed: 18754654
Annu Rev Pathol. 2009;4:127-50
pubmed: 18767981
Cancer Biol Ther. 2008 Sep;7(9):1321-5
pubmed: 18836294
J Clin Invest. 2008 Dec;118(12):3835-7
pubmed: 19033652
Adv Enzyme Regul. 2009;49(1):190-6
pubmed: 19168090
Cancer Res. 2009 Apr 15;69(8):3256-61
pubmed: 19351834
Immunity. 2009 May;30(5):696-707
pubmed: 19409814
Science. 2009 May 22;324(5930):1029-33
pubmed: 19460998
Nat Protoc. 2009;4(10):1513-21
pubmed: 19798084
Oncogene. 2010 Feb 4;29(5):687-97
pubmed: 19915616
Cancer Biol Ther. 2010 Jan;9(2):109-10
pubmed: 19949311
Cold Spring Harb Perspect Biol. 2009 Oct;1(4):a000067
pubmed: 20066093
Mol Cancer Ther. 2010 Jul;9(7):1956-67
pubmed: 20571069
Cell Signal. 2011 Feb;23(2):317-23
pubmed: 20727968
BMC Res Notes. 2010 Nov 10;3:294
pubmed: 21067583
Cancer Cell. 2011 Jan 18;19(1):58-71
pubmed: 21215704
J Biol Chem. 2011 Apr 1;286(13):11672-84
pubmed: 21224385
Cancer Res. 2011 Apr 15;71(8):2821-5
pubmed: 21385900
Biotechniques. 2011 Feb;50(2):98-115
pubmed: 21486251
Hum Mol Genet. 2011 Nov 1;20(21):4132-42
pubmed: 21828076
Genes Dev. 2011 Aug 15;25(16):1716-33
pubmed: 21852536
Annu Rev Cell Dev Biol. 2011;27:441-64
pubmed: 21985671
Cell Mol Life Sci. 2012 May;69(9):1475-91
pubmed: 22076652
Nature. 2011 Dec 21;481(7381):365-70
pubmed: 22190034
Mol Cell. 2011 Dec 23;44(6):846-8
pubmed: 22195959
FASEB J. 1990 Nov;4(14):3224-33
pubmed: 2227213
Sci Signal. 2012 Feb 28;5(213):ra18
pubmed: 22375056
Cancer Discov. 2011 Jul;1(2):103-5
pubmed: 22586351
Clin Cancer Res. 2012 Sep 1;18(17):4669-81
pubmed: 22806876
Cell. 2012 Jul 20;150(2):413-25
pubmed: 22817900
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
PLoS One. 2012;7(9):e45806
pubmed: 23049865
Nature. 2012 Nov 15;491(7424):364-73
pubmed: 23151579
Nat Rev Clin Oncol. 2013 Mar;10(3):143-53
pubmed: 23400000
Cell Death Dis. 2013 Mar 07;4:e532
pubmed: 23470539
Cancer Res. 2013 Aug 15;73(16):5218-31
pubmed: 23774212
J Biol Chem. 2013 Oct 11;288(41):29821-35
pubmed: 23963458
Exp Mol Med. 2013 Oct 04;45:e45
pubmed: 24091747
Nucleic Acids Res. 2014 Mar;42(5):3177-93
pubmed: 24353314
Nature. 2014 Apr 3;508(7494):118-22
pubmed: 24670642
J Urol. 2014 Sep;192(3):940-6
pubmed: 24704020
Bioinformatics. 2014 Sep 1;30(17):2524-6
pubmed: 24794931
J Biol Chem. 2014 Jun 13;289(24):16615-23
pubmed: 24798336
Nat Struct Mol Biol. 2014 Jun;21(6):522-7
pubmed: 24814346
ACS Med Chem Lett. 2011 Aug 26;2(10):774-9
pubmed: 24900266
Nat Commun. 2014 Jun 13;5:4153
pubmed: 24923787
Oncotarget. 2014 Aug 30;5(16):6670-86
pubmed: 25115398
Cell Rep. 2014 Sep 11;8(5):1461-74
pubmed: 25176644
Metabolism. 1989 Nov;38(11):1124-44
pubmed: 2554095
Cell Rep. 2015 Mar 31;10(12):2055-68
pubmed: 25801032
Cell Rep. 2015 Apr 7;11(1):98-110
pubmed: 25843712
Nat Commun. 2016 Feb 12;7:10689
pubmed: 26869029
PLoS One. 2016 Feb 26;11(2):e0149995
pubmed: 26919188
J Immunol. 2016 Jun 15;196(12):4987-98
pubmed: 27183586
Nat Commun. 2016 Oct 03;7:12969
pubmed: 27694884
Oncotarget. 2016 Dec 20;7(51):84054-84071
pubmed: 27863432
Cell Rep. 2016 Nov 22;17(9):2488-2501
pubmed: 27880917
Cell Signal. 2017 Jun;34:23-37
pubmed: 28235572
Development. 2017 Nov 15;144(22):4183-4194
pubmed: 29038306
Nat Commun. 2017 Nov 15;8(1):1508
pubmed: 29142193
J Biol Chem. 1968 Feb 25;243(4):844-7
pubmed: 4295607
Proc Natl Acad Sci U S A. 1969 Jan;62(1):234-41
pubmed: 4306045
Biochem J. 1974 Sep;141(3):761-74
pubmed: 4478069
Biochem Biophys Res Commun. 1979 Mar 15;87(1):244-52
pubmed: 454401
Nature. 1995 Dec 21-28;378(6559):785-9
pubmed: 8524413
J Biol Chem. 1996 Mar 1;271(9):4573-6
pubmed: 8617712
Oncogene. 1996 Jun 6;12(11):2251-7
pubmed: 8649764
Oncogene. 1996 Jul 4;13(1):21-9
pubmed: 8700549
Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11400-6
pubmed: 8876147
Science. 1997 Mar 28;275(5308):1943-7
pubmed: 9072974
Nat Genet. 1997 Apr;15(4):356-62
pubmed: 9090379
Biochem Biophys Res Commun. 1997 May 19;234(2):424-31
pubmed: 9177287
Cancer Res. 1997 Jun 1;57(11):2124-9
pubmed: 9187108
Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9052-7
pubmed: 9256433
Adv Second Messenger Phosphoprotein Res. 1997;31:105-11
pubmed: 9344245
Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1455-9
pubmed: 9465036
J Biol Chem. 1998 May 29;273(22):13375-8
pubmed: 9593664
Cell. 1998 Oct 2;95(1):29-39
pubmed: 9778245
Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13513-8
pubmed: 9811831
Genes Cells. 1998 Nov;3(11):697-707
pubmed: 9990505

Auteurs

Nilanjana Chatterjee (N)

Department 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 Pazarentzos (E)

Department 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 Mayekar (MK)

Department 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 Gui (P)

Department 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 Allegakoen (DV)

Department 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 Hrustanovic (G)

Department 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 Olivas (V)

Department 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 Lin (L)

Department 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 Verschueren (E)

J. 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 Johnson (JR)

J. 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 Hofree (M)

Department of Bioengineering, University of California, San Diego, San Diego, CA 92093, USA.

Jenny J Yan (JJ)

Department 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 Newton (BW)

J. 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 Dollen (JV)

J. 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 Earnshaw (CH)

Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.

Jennifer Flanagan (J)

Department 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 Chan (E)

Department 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 Asthana (S)

Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.

Trey Ideker (T)

Department of Bioengineering, University of California, San Diego, San Diego, CA 92093, USA.

Wei Wu (W)

Department 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 Suzuki (J)

Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.

Benjamin A Barad (BA)

Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA.

Yuriy Kirichok (Y)

Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.

James S Fraser (JS)

Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA.

William A Weiss (WA)

Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA.

Nevan J Krogan (NJ)

J. 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 Tulpule (A)

Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.

Amit J Sabnis (AJ)

Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.

Trever G Bivona (TG)

Department 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.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Synthetic Essentiality of Metabolic Regulator...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Synthetic Essentiality of Metabolic Regulator...
questionsmedicales.fr › Métabolisme › Voies et réseaux métaboliques › Glycolyse › Synthetic Essentiality of Metabolic Regulator...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › Synthetic Essentiality of Metabolic Regulator...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Synthetic Essentiality of Metabolic Regulator...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Synthetic Essentiality of Metabolic Regulator...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée NOD › Synthetic Essentiality of Metabolic Regulator...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souches mutantes de souris › Souris SCID › Synthetic Essentiality of Metabolic Regulator...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteur de transcription NF-kappa B › Synthetic Essentiality of Metabolic Regulator...
questionsmedicales.fr › Tumeurs › Synthetic Essentiality of Metabolic Regulator...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Phosphohydrolase PTEN › Synthetic Essentiality of Metabolic Regulator...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Pyruvate dehydrogenase acetyl-transferring kinase › Synthetic Essentiality of Metabolic Regulator...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines de répression › Synthetic Essentiality of Metabolic Regulator...