AMPK Promotes SPOP-Mediated NANOG Degradation to Regulate Prostate Cancer Cell Stemness.

AMP-Activated Protein Kinases / metabolism Animals Cell Line, Tumor Cullin Proteins / metabolism Genes, Tumor Suppressor Humans Male Mice, Nude Mutation / genetics Nanog Homeobox Protein / metabolism Nuclear Proteins / metabolism Prostatic Neoplasms / genetics Repressor Proteins / metabolism Transcription Factors / metabolism Ubiquitination / physiology
AMPK-BRAF axis NANOG SPOP prostate cancer stem cell ubiquitination

Journal

Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028

Informations de publication

Date de publication:
11 02 2019
Historique:
received: 22 05 2018
revised: 11 09 2018
accepted: 27 11 2018
pubmed: 1 1 2019
medline: 2 8 2019
entrez: 1 1 2019
Statut: ppublish

Résumé

NANOG is an essential transcriptional factor for the maintenance of embryonic stem cells (ESCs) and cancer stem cells (CSCs) in prostate cancer (PCa). However, the regulation mechanism of NANOG protein stability in cancer progression is still elusive. Here, we report that NANOG is degraded by SPOP, a frequently mutated tumor suppressor of PCa. Cancer-associated mutations of SPOP or the mutation of NANOG at S68Y abrogates the SPOP-mediated NANOG degradation, leading to elevated PCa cancer stemness and poor prognosis. In addition, SPOP-mediated NANOG degradation is controlled by the AMPK-BRAF signal axis through the phosphorylation of NANOG at Ser68, which blocked the interaction between SPOP and NANOG. Thus, our study provides a regulation mechanism of PCa stemness controlled by phosphorylation-mediated NANOG stability, which helps to identify novel drug targets and improve therapeutic strategy for PCa.

Identifiants

DOI: 10.1016/j.devcel.2018.11.033 PMID: 30595535 PMC: PMC7523188
pubmed: 30595535
pii: S1534-5807(18)31016-5
doi: 10.1016/j.devcel.2018.11.033
pmc: PMC7523188
mid: NIHMS1627382
pii:
doi:

Substances chimiques

Cullin Proteins 0
NANOG protein, human 0
Nanog Homeobox Protein 0
Nuclear Proteins 0
Repressor Proteins 0
SPOP protein, human 0
Transcription Factors 0
AMP-Activated Protein Kinases EC 2.7.11.31

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Pagination

345-360.e7

Subventions

Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States

Informations de copyright

Copyright © 2018 Elsevier Inc. All rights reserved.

Références

Mol Cell Biochem. 2010 Jul;340(1-2):265-73
pubmed: 20224986
Mol Cell. 2013 Oct 24;52(2):161-72
pubmed: 24095280
Stem Cells. 2009 May;27(5):993-1005
pubmed: 19415763
Mol Cell. 2009 Oct 9;36(1):39-50
pubmed: 19818708
Cell Rep. 2016 May 31;15(9):2012-24
pubmed: 27210749
Mol Cell. 2015 Sep 17;59(6):917-30
pubmed: 26344095
EMBO J. 2010 Aug 4;29(15):2646-58
pubmed: 20581804
Cancer Res. 2011 Jul 1;71(13):4640-52
pubmed: 21712410
Cell. 2010 Jan 8;140(1):62-73
pubmed: 20074520
Cancer Res. 2007 Sep 15;67(18):8671-81
pubmed: 17875707
EMBO J. 2016 Jun 15;35(12):1254-75
pubmed: 27220849
Prostate. 2014 Apr;74(4):381-94
pubmed: 24318967
Int J Cancer. 2014 Dec 15;135(12):2741-8
pubmed: 24375318
Oncogene. 2011 Sep 8;30(36):3833-45
pubmed: 21499299
Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14477-82
pubmed: 16973750
Science. 2014 Jan 3;343(6166):84-87
pubmed: 24336571
Development. 2009 Jul;136(14):2311-22
pubmed: 19542351
Cancer Res. 2014 Oct 1;74(19):5631-43
pubmed: 25274033
Mol Cancer. 2011 Sep 23;10:118
pubmed: 21943101
Hum Mutat. 2014 Sep;35(9):1142-51
pubmed: 24990631
Cell Metab. 2016 Jan 12;23(1):206-19
pubmed: 26724859
Nat Med. 2017 Sep;23(9):1063-1071
pubmed: 28805820
Cancer Res. 2003 Sep 15;63(18):5821-8
pubmed: 14522905
Cancer Prev Res (Phila). 2008 Oct;1(5):369-75
pubmed: 19138981
Biochem J. 2008 Jun 1;412(2):211-21
pubmed: 18387000
J Biol Chem. 2010 Jun 11;285(24):18858-67
pubmed: 20388706
Oncol Lett. 2014 Sep;8(3):985-992
pubmed: 25120646
Cell Stem Cell. 2008 Apr 10;2(4):333-44
pubmed: 18397753
Oncogene. 2011 Oct 20;30(42):4350-64
pubmed: 21577200
Science. 2013 Mar 29;339(6127):1567-70
pubmed: 23539597
EMBO Mol Med. 2014 Apr;6(4):519-38
pubmed: 24497570
Oncotarget. 2015 Sep 8;6(26):22361-74
pubmed: 26087476
Cell. 2003 May 30;113(5):631-42
pubmed: 12787504
Nature. 2014 Jul 10;511(7508):246-50
pubmed: 24909994
Breast Cancer Res. 2004;6(6):R605-15
pubmed: 15535842
Nat Cell Biol. 2015 Apr;17(4):490-9
pubmed: 25751139
Cell Stem Cell. 2012 Dec 7;11(6):783-98
pubmed: 23103054
Cell Death Dis. 2014 Jan 30;5:e1032
pubmed: 24481446
Neoplasia. 2014 Jan;16(1):14-20
pubmed: 24563616
Cell. 2015 Nov 5;163(4):1011-25
pubmed: 26544944
Science. 2014 Oct 3;346(6205):85-89
pubmed: 25278611
Mol Cell. 2015 Sep 17;59(6):904-16
pubmed: 26344096
Nature. 2007 Jan 4;445(7123):106-10
pubmed: 17122772
Oncol Lett. 2010 May;1(3):457-463
pubmed: 22966326
Cell Stem Cell. 2014 Mar 6;14(3):275-91
pubmed: 24607403
Oncogene. 2006 Mar 16;25(12):1696-708
pubmed: 16449977
Prostate. 2011 Jan 1;71(1):18-25
pubmed: 20583131
Cancer Res. 2009 Oct 1;69(19):7507-11
pubmed: 19752085
Nat Med. 2017 Sep;23(9):1046-1054
pubmed: 28805821
Stem Cell Reports. 2014 Jan 14;2(1):18-25
pubmed: 24678451
Cell Rep. 2014 Feb 27;6(4):657-69
pubmed: 24508459
Nat Med. 2017 Sep;23(9):1055-1062
pubmed: 28805822
Genes Dev. 2009 Mar 1;23(5):537-48
pubmed: 19270154
CA Cancer J Clin. 2013 Jan;63(1):11-30
pubmed: 23335087
Nature. 2018 Jan 4;553(7686):91-95
pubmed: 29160310
Nat Genet. 2012 May 20;44(6):685-9
pubmed: 22610119
Cell. 2003 May 30;113(5):643-55
pubmed: 12787505

Auteurs

Xinbo Wang (X)

Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China; Shanghai Putuo People's Hospital, School of Medicine, Tongji University, Shanghai 200060, China; Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.

Jiali Jin (J)

Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China; Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.

Fangning Wan (F)

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.

Linlin Zhao (L)

Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China; Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.

Hongshang Chu (H)

Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.

Cong Chen (C)

Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.

Guanghong Liao (G)

Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.

Jian Liu (J)

National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Yue Yu (Y)

Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.

Hongqi Teng (H)

Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.

Lan Fang (L)

Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.

Cong Jiang (C)

Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.

Weijuan Pan (W)

Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.

Xin Xie (X)

National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Jia Li (J)

National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Xiaolin Lu (X)

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.

Xuejun Jiang (X)

Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

Xin Ge (X)

Department of Clinical Medicine, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China. Electronic address: xin.ge@tongji.edu.cn.

Dingwei Ye (D)

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: dwyeli@163.com.

Ping Wang (P)

Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China. Electronic address: wangp@tongji.edu.cn.

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 › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › AMP-Activated Protein Kinases › AMPK Promotes SPOP-Mediated NANOG Degradation...
questionsmedicales.fr › Eucaryotes › Animaux › AMPK Promotes SPOP-Mediated NANOG Degradation...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › AMPK Promotes SPOP-Mediated NANOG Degradation...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cycle cellulaire › Cullines › AMPK Promotes SPOP-Mediated NANOG Degradation...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Gènes suppresseurs de tumeur › AMPK Promotes SPOP-Mediated NANOG Degradation...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › AMPK Promotes SPOP-Mediated NANOG Degradation...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souches mutantes de souris › Souris nude › AMPK Promotes SPOP-Mediated NANOG Degradation...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › AMPK Promotes SPOP-Mediated NANOG Degradation...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéine homéotique Nanog › AMPK Promotes SPOP-Mediated NANOG Degradation...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines nucléaires › AMPK Promotes SPOP-Mediated NANOG Degradation...
questionsmedicales.fr › Maladies urogénitales › Tumeurs de l'appareil urogénital › Tumeurs de l'appareil génital mâle › Tumeurs de la prostate › AMPK Promotes SPOP-Mediated NANOG Degradation...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines de répression › AMPK Promotes SPOP-Mediated NANOG Degradation...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › AMPK Promotes SPOP-Mediated NANOG Degradation...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Modification traductionnelle des protéines › Maturation post-traductionnelle des protéines › Ubiquitination › AMPK Promotes SPOP-Mediated NANOG Degradation...