Targeting the cyclin-dependent kinase 5 in metastatic melanoma.

Animals Cell Line, Tumor Cell Movement / drug effects Cyclin-Dependent Kinase 5 / antagonists & inhibitors Female Gene Dosage Humans Male Melanoma / drug therapy Melanoma, Experimental / drug therapy Mice Mice, Knockout Phosphorylation / drug effects Prognosis Skin / pathology Skin Neoplasms / drug therapy Vimentin / metabolism Xenograft Model Antitumor Assays
CDK5 cyclin-dependent kinases metastasis mouse cancer models

Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
07 04 2020
Historique:
pubmed: 21 3 2020
medline: 21 7 2020
entrez: 21 3 2020
Statut: ppublish

Résumé

The cyclin-dependent kinase 5 (CDK5), originally described as a neuronal-specific kinase, is also frequently activated in human cancers. Using conditional CDK5 knockout mice and a mouse model of highly metastatic melanoma, we found that CDK5 is dispensable for the growth of primary tumors. However, we observed that ablation of CDK5 completely abrogated the metastasis, revealing that CDK5 is essential for the metastatic spread. In mouse and human melanoma cells CDK5 promotes cell invasiveness by directly phosphorylating an intermediate filament protein, vimentin, thereby inhibiting assembly of vimentin filaments. Chemical inhibition of CDK5 blocks the metastatic spread of patient-derived melanomas in patient-derived xenograft (PDX) mouse models. Hence, inhibition of CDK5 might represent a very potent therapeutic strategy to impede the metastatic dissemination of malignant cells.

Identifiants

DOI: 10.1073/pnas.1912617117 PMID: 32193336 PMC: PMC7149478
pubmed: 32193336
pii: 1912617117
doi: 10.1073/pnas.1912617117
pmc: PMC7149478
doi:

Substances chimiques

VIM protein, human 0
Vim protein, mouse 0
Vimentin 0
Cyclin-Dependent Kinase 5 EC 2.7.11.1
CDK5 protein, human EC 2.7.11.22
Cdk5 protein, mouse EC 2.7.11.22

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

8001-8012

Subventions

Organisme : NCI NIH HHS
ID : P30 CA010815
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA243769
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA202634
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA239660
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM132129
Pays : United States

Déclaration de conflit d'intérêts

Competing interest statement: P.S. has been a consultant at Novartis, Genovis, Guidepoint, The Planning Shop, ORIC Pharmaceuticals, and Exo Therapeutics; his laboratory receives research funding from Novartis. W.M. is currently an employee of Cedilla Therapeutics.

Références

World J Surg Oncol. 2016 Feb 09;14(1):34
pubmed: 26860827
Cancer Res. 2006 Aug 1;66(15):7509-15
pubmed: 16885348
Nat Cell Biol. 2006 Feb;8(2):156-62
pubmed: 16429129
Cell Rep. 2017 Nov 14;21(7):1936-1952
pubmed: 29141224
Dev Growth Differ. 2014 Jun;56(5):335-48
pubmed: 24844647
Nature. 2000 Sep 21;407(6802):395-401
pubmed: 11014197
Transl Oncol. 2015 Aug;8(4):295-307
pubmed: 26310376
J Biol Chem. 1988 Apr 25;263(12):5970-8
pubmed: 2833525
Cancer Metastasis Rev. 2005 Jan;24(1):165-83
pubmed: 15785879
Science. 2016 Jul 22;353(6297):399-403
pubmed: 27463676
PLoS Genet. 2013 Jun;9(6):e1003531
pubmed: 23785295
Clin Cancer Res. 2011 Oct 1;17(19):6140-50
pubmed: 21825040
Nat Rev Cancer. 2009 Mar;9(3):153-66
pubmed: 19238148
Cancer Cell. 2013 Oct 14;24(4):499-511
pubmed: 24135281
Oncogene. 2008 Jul 31;27(33):4615-24
pubmed: 18391978
J Cell Biol. 2014 Dec 8;207(5):627-42
pubmed: 25452387
J Biol Chem. 1996 Aug 23;271(34):20608-16
pubmed: 8702807
Med Oncol. 2011 Sep;28(3):673-8
pubmed: 20354813
Anal Chem. 2012 Nov 6;84(21):9214-21
pubmed: 23098179
Neuron. 2007 Dec 6;56(5):823-37
pubmed: 18054859
Nat Cell Biol. 2009 May;11(5):624-30
pubmed: 19363486
Trends Cancer. 2019 May;5(5):308-324
pubmed: 31174843
Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3565-70
pubmed: 9108016
Curr Biol. 1998 Feb 26;8(5):257-66
pubmed: 9501066
Cancer Discov. 2016 Apr;6(4):353-67
pubmed: 26658964
Trends Cancer. 2016 Oct;2(10):606-618
pubmed: 27917404
Ann Surg Oncol. 2000 May;7(4):262-7
pubmed: 10819365
J Biol Chem. 1998 Sep 11;273(37):24057-64
pubmed: 9727024
Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11173-8
pubmed: 8855328
Nat Rev Cancer. 2006 Jun;6(6):449-58
pubmed: 16723991
Br Med Bull. 2014 Sep;111(1):149-62
pubmed: 25190764
J Biol Chem. 1995 Oct 6;270(40):23589-97
pubmed: 7559524
Oncol Rep. 2019 Feb;41(2):779-788
pubmed: 30431123
Mol Cancer. 2010 Jul 31;9:204
pubmed: 20673369
Cell Rep. 2017 Nov 14;21(7):1953-1967
pubmed: 29141225
Cell Mol Life Sci. 2011 Sep;68(18):3033-46
pubmed: 21637948
Genes Dev. 2016 Jan 1;30(1):18-33
pubmed: 26679841
Proc Natl Acad Sci U S A. 1989 Mar;86(6):1885-9
pubmed: 2648386
Nat Neurosci. 2007 Jul;10(7):880-886
pubmed: 17529984
Eur J Biochem. 1997 Jan 15;243(1-2):527-36
pubmed: 9030781
Cancers (Basel). 2019 Apr 12;11(4):
pubmed: 31013770
Oncotarget. 2015 May 20;6(14):12080-93
pubmed: 25900242
Nature. 1987 Aug 13-19;328(6131):649-52
pubmed: 3039376
Biochim Biophys Acta. 2013 Jun;1833(6):1283-93
pubmed: 23458836
Exp Cell Res. 2007 Jun 10;313(10):2050-62
pubmed: 17512929
Pathology. 1985 Apr;17(2):340-5
pubmed: 2995906
J Dermatol. 2004 Apr;31(4):299-304
pubmed: 15187325
Genome Biol. 2014;15(6):122
pubmed: 25180339
J Cell Physiol. 2012 Feb;227(2):739-50
pubmed: 21465480
Anal Chem. 2012 Sep 4;84(17):7469-78
pubmed: 22880955
J Biol Chem. 2007 Feb 2;282(5):2776-84
pubmed: 17145757
Nat Rev Cancer. 2017 Jan 27;17(2):93-115
pubmed: 28127048
J Cell Sci. 2004 Feb 29;117(Pt 6):919-32
pubmed: 14762106
Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1442-7
pubmed: 18234856
Nat Rev Mol Cell Biol. 2001 Oct;2(10):749-59
pubmed: 11584302
J Cancer. 2016 May 25;7(9):1049-56
pubmed: 27326247
Chem Biol. 2002 Jan;9(1):25-33
pubmed: 11841936
Cell. 1990 Sep 21;62(6):1063-71
pubmed: 2169348
Exp Cell Res. 2015 Jan 1;330(1):186-98
pubmed: 25128817
Cell. 2012 Jul 20;150(2):251-63
pubmed: 22817889
Cancer Cell. 2011 Dec 13;20(6):741-54
pubmed: 22172720
Proc Natl Acad Sci U S A. 2008 May 27;105(21):7570-5
pubmed: 18487454
Development. 1993 Dec;119(4):1029-40
pubmed: 8306873
Nat Rev Cancer. 2003 Aug;3(8):559-70
pubmed: 12894244
Sci Rep. 2013 Oct 14;3:2932
pubmed: 24121667
Oncotarget. 2017 Nov 26;8(65):108333-108354
pubmed: 29312535
Cancer Res. 2010 Jun 1;70(11):4460-9
pubmed: 20484029
Clin Cancer Res. 2015 Mar 15;21(6):1419-28
pubmed: 25609066
J Biol Chem. 2017 Apr 14;292(15):6269-6280
pubmed: 28242758
Exp Cell Res. 2015 Jul 1;335(1):115-22
pubmed: 25959509
FASEB J. 2019 Jan;33(1):631-642
pubmed: 30040488
Exp Cell Res. 2007 Jun 10;313(10):2098-109
pubmed: 17498690
Mol Cell Biochem. 2018 Jan;438(1-2):47-57
pubmed: 28744809
Curr Protoc Chem Biol. 2010 Mar 1;2(1):15-36
pubmed: 23836541
Development. 2013 Aug;140(15):3079-93
pubmed: 23861057
J Biol Chem. 1991 Apr 25;266(12):7325-8
pubmed: 2019567
Nat Genet. 2009 May;41(5):544-52
pubmed: 19282848
J Neurosci. 2001 Sep 1;21(17):6758-71
pubmed: 11517264

Auteurs

Samanta Sharma (S)

Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215.
Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115.

Tian Zhang (T)

Department of Cell Biology, Harvard Medical School, Boston, MA 02115.

Wojciech Michowski (W)

Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215.
Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115.

Vito W Rebecca (VW)

Oncogenesis Program, The Wistar Institute, Philadelphia, PA 19104.

Min Xiao (M)

Oncogenesis Program, The Wistar Institute, Philadelphia, PA 19104.

Roberta Ferretti (R)

David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Translational Innovation Platform Oncology, Emmanuel Merck Darmstadt (EMD) Serono Research and Development Institute, Inc., Billerica, MA 01821.

Jan M Suski (JM)

Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215.
Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115.

Roderick T Bronson (RT)

Rodent Histopathology Core, Harvard Medical School, Boston, MA 02115.

Joao A Paulo (JA)

Department of Cell Biology, Harvard Medical School, Boston, MA 02115.

Dennie Frederick (D)

Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.

Anne Fassl (A)

Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215.
Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115.

Genevieve M Boland (GM)

Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.

Yan Geng (Y)

Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215.
Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115.

Jacqueline A Lees (JA)

David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.

Rene H Medema (RH)

Division of Cell Biology, Oncode Institute, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.

Meenhard Herlyn (M)

Oncogenesis Program, The Wistar Institute, Philadelphia, PA 19104.

Steven P Gygi (SP)

Department of Cell Biology, Harvard Medical School, Boston, MA 02115.

Piotr Sicinski (P)

Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215; peter_sicinski@dfci.harvard.edu.
Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115.

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 › Targeting the cyclin-dependent kinase 5 in...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Targeting the cyclin-dependent kinase 5 in...
questionsmedicales.fr › Phénomènes physiologiques › Mouvement cellulaire › Targeting the cyclin-dependent kinase 5 in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Proline-directed protein kinases › Kinases cyclines-dépendantes › Kinases CDC2-CDC28 › Kinase-5 cycline-dépendante › Targeting the cyclin-dependent kinase 5 in...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Dosage génique › Targeting the cyclin-dependent kinase 5 in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Targeting the cyclin-dependent kinase 5 in...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Naevus et mélanomes › Mélanome › Targeting the cyclin-dependent kinase 5 in...
questionsmedicales.fr › Techniques d'investigation › Modèles animaux › Tumeurs expérimentales › Mélanome expérimental › Targeting the cyclin-dependent kinase 5 in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Targeting the cyclin-dependent kinase 5 in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Targeting the cyclin-dependent kinase 5 in...
questionsmedicales.fr › Métabolisme › Phosphorylation › Targeting the cyclin-dependent kinase 5 in...
questionsmedicales.fr › Diagnostic › Pronostic › Targeting the cyclin-dependent kinase 5 in...
questionsmedicales.fr › Système tégumentaire › Peau › Targeting the cyclin-dependent kinase 5 in...
questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Tumeurs cutanées › Targeting the cyclin-dependent kinase 5 in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cytosquelette › Protéines de filaments intermédiaires › Vimentine › Targeting the cyclin-dependent kinase 5 in...
questionsmedicales.fr › Techniques d'investigation › Transplantation tumorale › Tests d'activité antitumorale sur modèle de xénogreffe › Targeting the cyclin-dependent kinase 5 in...