G1/S cell cycle regulators mediate effects of circadian dysregulation on tumor growth and provide targets for timed anticancer treatment.
Animals
Cell Cycle
/ physiology
Cell Division
/ physiology
Cell Line
Chronobiology Disorders
/ metabolism
Circadian Rhythm
/ physiology
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinase 6
Cyclin-Dependent Kinases
/ metabolism
G1 Phase
/ physiology
Humans
Male
Mice
Mice, Inbred C57BL
Neoplasms
/ metabolism
Phosphorylation
Proto-Oncogene Proteins
/ genetics
Retinoblastoma Protein
S Phase
/ physiology
Journal
PLoS biology
ISSN: 1545-7885
Titre abrégé: PLoS Biol
Pays: United States
ID NLM: 101183755
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
20
09
2018
accepted:
27
03
2019
entrez:
1
5
2019
pubmed:
1
5
2019
medline:
7
1
2020
Statut:
epublish
Résumé
Circadian disruption has multiple pathological consequences, but the underlying mechanisms are largely unknown. To address such mechanisms, we subjected transformed cultured cells to chronic circadian desynchrony (CCD), mimicking a chronic jet-lag scheme, and assayed a range of cellular functions. The results indicated a specific circadian clock-dependent increase in cell proliferation. Transcriptome analysis revealed up-regulation of G1/S phase transition genes (myelocytomatosis oncogene cellular homolog [Myc], cyclin D1/3, chromatin licensing and DNA replication factor 1 [Cdt1]), concomitant with increased phosphorylation of the retinoblastoma (RB) protein by cyclin-dependent kinase (CDK) 4/6 and increased G1-S progression. Phospho-RB (Ser807/811) was found to oscillate in a circadian fashion and exhibit phase-shifted rhythms in circadian desynchronized cells. Consistent with circadian regulation, a CDK4/6 inhibitor approved for cancer treatment reduced growth of cultured cells and mouse tumors in a time-of-day-specific manner. Our study identifies a mechanism that underlies effects of circadian disruption on tumor growth and underscores the use of treatment timed to endogenous circadian rhythms.
Identifiants
pubmed: 31039152
doi: 10.1371/journal.pbio.3000228
pii: PBIOLOGY-D-18-00754
pmc: PMC6490878
doi:
Substances chimiques
Proto-Oncogene Proteins
0
Retinoblastoma Protein
0
CDK4 protein, human
EC 2.7.11.22
CDK6 protein, human
EC 2.7.11.22
Cyclin-Dependent Kinase 4
EC 2.7.11.22
Cyclin-Dependent Kinase 6
EC 2.7.11.22
Cyclin-Dependent Kinases
EC 2.7.11.22
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
e3000228Subventions
Organisme : NINDS NIH HHS
ID : R37 NS048471
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
J Clin Invest. 2010 Jul;120(7):2600-9
pubmed: 20577050
Int J Mol Sci. 2017 Oct 17;18(10):
pubmed: 29039812
Front Neurol. 2015 May 11;6:96
pubmed: 26029155
Oncotarget. 2017 Jun 28;8(40):67670-67683
pubmed: 28978062
PLoS Biol. 2014 Apr 15;12(4):e1001840
pubmed: 24737000
Exp Cell Res. 1999 Apr 10;248(1):110-4
pubmed: 10094818
J Biol Chem. 2002 Aug 23;277(34):31263-9
pubmed: 12070150
Gut. 2017 Jul;66(7):1286-1296
pubmed: 27849562
Cancer Res. 2004 Nov 1;64(21):7879-85
pubmed: 15520194
Cancer Cell. 2012 Oct 16;22(4):438-51
pubmed: 23079655
Oncotarget. 2017 May 23;8(21):34128-34140
pubmed: 28388556
Proc Natl Acad Sci U S A. 2016 Nov 22;113(47):13516-13521
pubmed: 27834218
Genomics. 2001 Dec;78(3):129-34
pubmed: 11735219
Cell Metab. 2017 Jan 10;25(1):118-127
pubmed: 27818261
J Cell Sci. 2010 Oct 15;123(Pt 20):3547-57
pubmed: 20930143
N Engl J Med. 2015 Oct 22;373(17):1672-3
pubmed: 26488700
Nature. 2018 Jan 18;553(7688):351-355
pubmed: 29320480
PLoS Genet. 2014 May 29;10(5):e1004338
pubmed: 24875049
J Biol Chem. 2008 Feb 22;283(8):4535-42
pubmed: 18086663
Methods Mol Biol. 2014;1170:449-61
pubmed: 24906329
Blood. 2004 Dec 1;104(12):3697-704
pubmed: 15292061
Int J Alzheimers Dis. 2011;2011:832379
pubmed: 22191060
Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5523-7
pubmed: 1648218
Lancet Oncol. 2015 Jan;16(1):25-35
pubmed: 25524798
Sci Rep. 2017 Apr 20;7(1):985
pubmed: 28428557
Elife. 2014 Jun 04;3:
pubmed: 24876129
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
J Natl Cancer Inst. 2001 Nov 21;93(22):1739-46
pubmed: 11717335
Free Radic Biol Med. 2018 May 1;119:129-138
pubmed: 29277444
Prog Mol Biol Transl Sci. 2013;119:221-82
pubmed: 23899600
Cell. 2016 May 5;165(4):896-909
pubmed: 27153497
Cell. 2004 Apr 16;117(2):239-51
pubmed: 15084261
Cell Rep. 2018 Mar 27;22(13):3416-3426
pubmed: 29590612
Cell Metab. 2017 Jan 10;25(1):102-117
pubmed: 27818260
Genes Cancer. 2012 Nov;3(11-12):619-33
pubmed: 23634251
Elife. 2015 Aug 29;4:
pubmed: 26319354
Trends Endocrinol Metab. 2016 Apr;27(4):192-203
pubmed: 26947521
Trends Cell Biol. 2018 May;28(5):368-379
pubmed: 29471986
Cancer Cell. 2016 Dec 12;30(6):909-924
pubmed: 27889186
Cancer Res. 2006 Nov 15;66(22):10720-8
pubmed: 17108108
Cell Div. 2012 Mar 14;7(1):10
pubmed: 22417103
Nat Rev Cancer. 2017 Jan 27;17(2):93-115
pubmed: 28127048
J Steroid Biochem Mol Biol. 2017 Jan;165(Pt A):114-120
pubmed: 27002803
Cell Metab. 2015 Dec 1;22(6):1009-19
pubmed: 26387865
Bioinformatics. 2016 Nov 1;32(21):3351-3353
pubmed: 27378304
Chronobiol Int. 2014 Mar;31(2):189-98
pubmed: 24147659
Science. 2016 Sep 2;353(6303):987-988
pubmed: 27701101
Cell Cycle. 2014;13(22):3611-7
pubmed: 25483096
Mol Cell. 2016 Nov 17;64(4):774-789
pubmed: 27840026
Nucleic Acids Res. 2013 Jan;41(Database issue):D1009-13
pubmed: 23180795
Clin Cancer Res. 2017 Oct 1;23(19):5802-5813
pubmed: 28637687
Cell. 2009 Oct 2;139(1):199-210
pubmed: 19765810
Cell Div. 2006 Oct 17;1:22
pubmed: 17042960
J Clin Immunol. 2013 Apr;33(3):540-9
pubmed: 23264026
Nature. 2017 Jun 15;546(7658):426-430
pubmed: 28607489
Cell Cycle. 2014;13(18):2879-88
pubmed: 25486476
Biochem Biophys Res Commun. 2003 Aug 29;308(3):646-54
pubmed: 12914799
J Physiol Paris. 2013 Sep;107(4):310-22
pubmed: 23545147
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Cell Metab. 2017 May 2;25(5):1206
pubmed: 28467936
Cancer Res. 2016 Apr 15;76(8):2301-13
pubmed: 27020857
Ann Med. 2014 Jun;46(4):191-207
pubmed: 24915535
Trends Biochem Sci. 2013 Jan;38(1):12-9
pubmed: 23218751
Cell. 2002 Oct 4;111(1):41-50
pubmed: 12372299
Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1592-9
pubmed: 23267082
Front Endocrinol (Lausanne). 2017 Apr 28;8:70
pubmed: 28503165
Nat Rev Clin Oncol. 2016 Jul;13(7):417-30
pubmed: 27030077
Sci Rep. 2017 Nov 24;7(1):16310
pubmed: 29176713
Oncotarget. 2018 Feb 20;9(18):14524-14538
pubmed: 29581861
Cell Metab. 2016 Aug 9;24(2):324-31
pubmed: 27476975
BMC Biol. 2017 Feb 14;15(1):13
pubmed: 28196531
Nat Rev Genet. 2017 Mar;18(3):164-179
pubmed: 27990019
PLoS Genet. 2009 Apr;5(4):e1000442
pubmed: 19343201
F1000Res. 2017 Oct 30;6:1910
pubmed: 29152229
Biochim Biophys Acta. 2011 May;1812(5):581-91
pubmed: 21320597
J Mol Med (Berl). 2016 Dec;94(12):1313-1326
pubmed: 27695879
Ann Med. 2014 Jun;46(4):221-32
pubmed: 24779962
Nat Rev Mol Cell Biol. 2013 Aug;14(8):518-28
pubmed: 23877564
J Biol Chem. 1997 May 9;272(19):12738-46
pubmed: 9139732
Int Arch Occup Environ Health. 2002 Aug;75(6):435-40
pubmed: 12070640
Sci Rep. 2015 Jun 15;5:11417
pubmed: 26073568
Nucleic Acids Res. 2017 Jan 4;45(D1):D635-D642
pubmed: 27899575
Science. 2000 Sep 29;289(5488):2344-7
pubmed: 11009419
Mol Biol Cell. 1997 Feb;8(2):287-301
pubmed: 9190208
Clin Transl Oncol. 2018 Sep;20(9):1136-1144
pubmed: 29564714
Endocr Rev. 2016 Oct;37(5):450-466
pubmed: 27712099
Science. 1996 Dec 6;274(5293):1672-7
pubmed: 8939849
Cold Spring Harb Perspect Biol. 2013 Mar 01;5(3):a008904
pubmed: 23457258
Int J Genomics. 2018 Jan 21;2018:8576890
pubmed: 29607311
Science. 2003 Oct 10;302(5643):255-9
pubmed: 12934012