The Cancer Aneuploidy Paradox: In the Light of Evolution.
aneuploidy
autokaryogamy
cancer
chromothripsis
cleavage embryo
disabled spindle
meio-mitosis
recombination on kinetochores
reduction
somatic pairing
Journal
Genes
ISSN: 2073-4425
Titre abrégé: Genes (Basel)
Pays: Switzerland
ID NLM: 101551097
Informations de publication
Date de publication:
25 01 2019
25 01 2019
Historique:
received:
07
01
2019
revised:
21
01
2019
accepted:
22
01
2019
entrez:
30
1
2019
pubmed:
30
1
2019
medline:
30
1
2019
Statut:
epublish
Résumé
Aneuploidy should compromise cellular proliferation but paradoxically favours tumour progression and poor prognosis. Here, we consider this paradox in terms of our most recent observations of chemo/radio-resistant cells undergoing reversible polyploidy. The latter perform the segregation of two parental groups of end-to-end linked dyads by pseudo-mitosis creating tetraploid cells through a dysfunctional spindle. This is followed by autokaryogamy and a homologous pairing preceding a bi-looped endo-prophase. The associated RAD51 and DMC1/γ-H2AX double-strand break repair foci are tandemly situated on the AURKB/REC8/kinetochore doublets along replicated chromosome loops, indicative of recombination events. MOS-associated REC8-positive peri-nucleolar centromere cluster organises a monopolar spindle. The process is completed by reduction divisions (bi-polar or by radial cytotomy including pedogamic exchanges) and by the release of secondary cells and/or the formation of an embryoid. Together this process preserves genomic integrity and chromosome pairing, while tolerating aneuploidy by by-passing the mitotic spindle checkpoint. Concurrently, it reduces the chromosome number and facilitates recombination that decreases the mutation load of aneuploidy and lethality in the chemo-resistant tumour cells. This cancer life-cycle has parallels both within the cycling polyploidy of the asexual life cycles of ancient unicellular protists and cleavage embryos of early multicellulars, supporting the atavistic theory of cancer.
Identifiants
pubmed: 30691027
pii: genes10020083
doi: 10.3390/genes10020083
pmc: PMC6409809
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
Références
Oncogene. 2017 Aug 24;36(34):4887-4900
pubmed: 28436947
Nat Rev Cancer. 2018 Dec;18(12):758-766
pubmed: 30420767
Cancer Biol Ther. 2004 Feb;3(2):207-18
pubmed: 14726689
Science. 2005 Dec 9;310(5754):1683-6
pubmed: 16339446
Stem Cells. 2012 May;30(5):833-44
pubmed: 22489015
Proc Natl Acad Sci U S A. 1981 Jan;78(1):377-81
pubmed: 6941253
Oncogene. 2010 Oct 7;29(40):5447-51
pubmed: 20676137
Mol Cytogenet. 2018 May 10;11:31
pubmed: 29760781
Am Nat. 2009 Jul;174 Suppl 1:S1-S14
pubmed: 19441962
Phys Rev Lett. 2005 Apr 1;94(12):128701
pubmed: 15903968
Br J Cancer. 2017 Apr 25;116(9):1186-1194
pubmed: 28334734
EMBO J. 2010 Apr 7;29(7):1272-84
pubmed: 20186124
Cancers (Basel). 2018 Aug 01;10(8):
pubmed: 30071623
Cell Biol Int. 2000;24(9):621-33
pubmed: 10964452
Genetics. 2009 Jan;181(1):3-12
pubmed: 19139151
Cell Biol Int. 2000;24(9):635-48
pubmed: 10964453
Proc Biol Sci. 2011 Jul 22;278(1715):2081-90
pubmed: 21429931
Oncoscience. 2014 Dec 17;2(1):3-14
pubmed: 25821840
Nat Rev Cancer. 2005 Aug;5(8):615-25
pubmed: 16034368
Oncotarget. 2016 Nov 15;7(46):75235-75260
pubmed: 27655693
R Soc Open Sci. 2018 Sep 19;5(9):180442
pubmed: 30839720
PLoS One. 2011;6(12):e28255
pubmed: 22164254
Exp Cell Res. 2010 Aug 1;316(13):2099-112
pubmed: 20457152
N Engl J Med. 2017 Jun 1;376(22):2109-2121
pubmed: 28445112
Mol Oncol. 2011 Aug;5(4):315-23
pubmed: 21852209
Genomics. 2010 Jun;95(6):345-54
pubmed: 20298777
Cell. 2014 Mar 27;157(1):267-71
pubmed: 24679541
Cancer Res. 2009 Mar 15;69(6):2296-304
pubmed: 19258501
Chromosoma. 1974 Mar 14;45(2):151-62
pubmed: 4135138
Cell Cycle. 2015;14(18):2969-84
pubmed: 26102294
Cell Biol Int. 2008 Sep;32(9):1044-56
pubmed: 18602486
Cell Biol Int. 2008 Sep;32(9):1031-43
pubmed: 18550395
Mol Cytogenet. 2016 Feb 13;9:15
pubmed: 26877768
Cancer Res. 2001 Jan 15;61(2):538-49
pubmed: 11212247
Oncotarget. 2015 Nov 24;6(37):40005-25
pubmed: 26503466
Cancer Discov. 2014 Feb;4(2):175-185
pubmed: 24436049
Adv Cancer Res. 2011;112:283-350
pubmed: 21925308
Exp Cell Res. 2009 Sep 10;315(15):2593-603
pubmed: 19463812
Philos Trans R Soc Lond B Biol Sci. 2016 Oct 19;371(1706):
pubmed: 27619705
Cell Biol Int. 1993 Oct;17(10):945-8
pubmed: 8287024
Nat Commun. 2015 Dec 07;6:10132
pubmed: 26640040
Cancer Immun. 2001 Mar 30;1:1
pubmed: 12747762
Cell Cycle. 2014;13(4):528-37
pubmed: 24299711
Br J Cancer. 2018 Jan;118(2):145-152
pubmed: 29337961
Cancer. 2011 Sep 1;117(17):4092-9
pubmed: 21365635
Curr Cancer Drug Targets. 2019;19(5):360-367
pubmed: 29968537
Genome Biol Evol. 2018 Nov 1;10(11):3118-3128
pubmed: 30380054
J Evol Biol. 2003 Mar;16(2):189-99
pubmed: 14635857
Nat Rev Genet. 2017 Jul;18(7):411-424
pubmed: 28502977
Int J Mol Sci. 2016 May 11;17(5):
pubmed: 27187358
Cell Biol Int. 2007 Dec;31(12):1507-10
pubmed: 17936649
Cell. 2017 Apr 6;169(2):229-242.e21
pubmed: 28388408
Cell Cycle. 2013 Feb 1;12(3):430-41
pubmed: 23287532
Proc Natl Acad Sci U S A. 2017 Jun 13;114(24):6406-6411
pubmed: 28484005
Cancer Res. 2018 May 1;78(9):2318-2331
pubmed: 29440172
J Cell Sci. 2003 Oct 15;116(Pt 20):4095-106
pubmed: 12953071
Nature. 2008 May 22;453(7194):544-7
pubmed: 18497826
New Phytol. 2015 Oct;208(2):306-23
pubmed: 26075313
Cell Death Dis. 2015 Apr 02;6:e1711
pubmed: 25837487
Genome Res. 2013 Jul;23(7):1054-62
pubmed: 23817046
J Cell Biol. 1981 Dec;91(3 Pt 1):743-55
pubmed: 7328119
Cell Discov. 2018 Oct 2;4:54
pubmed: 30302273
Trends Parasitol. 2016 Nov;32(11):855-862
pubmed: 27599632
J Skin Cancer. 2013;2013:190109
pubmed: 23840955
J Theor Biol. 1992 Jan 7;154(1):43-55
pubmed: 1573902
Mutat Res. 1964 May;106:2-9
pubmed: 14195748
Trends Cell Biol. 2017 Dec;27(12):917-930
pubmed: 28899600
Histochem Cell Biol. 2016 Apr;145(4):497-508
pubmed: 26860864
J Cell Biol. 1996 Sep;134(5):1109-25
pubmed: 8794855
Hum Pathol. 2013 Apr;44(4):472-9
pubmed: 23069255
Cancer Cell Int. 2005 Feb 16;5(1):4
pubmed: 15715909
Cancers (Basel). 2018 Apr 15;10(4):
pubmed: 29662021
Proc Biol Sci. 2010 Mar 22;277(1683):869-76
pubmed: 19923128
Cell Biol Int. 2005 Dec;29(12):1005-11
pubmed: 16314119
Cell Biol Int. 2011 Jul;35(7):687-95
pubmed: 21250945
Proc Natl Acad Sci U S A. 2015 Aug 18;112(33):10467-72
pubmed: 26240372
BMC Cancer. 2006 Jan 09;6:6
pubmed: 16401344
Int Rev Cell Mol Biol. 2018;337:1-48
pubmed: 29551157
Cell Cycle. 2009 Oct 1;8(19):3234-7
pubmed: 19738438
Mol Hum Reprod. 2003 Dec;9(12):749-56
pubmed: 14614036
Genetika. 2003 Apr;39(4):453-73
pubmed: 12760244
PLoS One. 2016 Dec 1;11(12):e0167503
pubmed: 27907204
Genes Dev. 2015 Dec 1;29(23):2405-19
pubmed: 26637526
Cancer Cell Int. 2013 Sep 11;13(1):92
pubmed: 24025698
Cell Biol Int. 2000;24(2):61-70
pubmed: 10772764
Oncogenesis. 2016 Dec 19;5(12):e281
pubmed: 27991913
An Acad Bras Cienc. 2003 Sep;75(3):285-300
pubmed: 12947479
Annu Rev Genet. 2015;49:183-211
pubmed: 26442848
Genetics. 1965 Jun;51:915-29
pubmed: 14337764
Nat Commun. 2014 Oct 08;5:4979
pubmed: 25296379
Nature. 2012 Jan 18;482(7383):53-8
pubmed: 22258507
Mol Cell Biol. 2001 Aug;21(16):5667-77
pubmed: 11463847
Cell Biol Int. 2005 Dec;29(12):1012-8
pubmed: 16310380
Nature. 1994 Jul 21;370(6486):213-6
pubmed: 8028667
Nat Cell Biol. 2019 Jan;21(1):94-101
pubmed: 30602768
Oncogene. 2014 Jan 2;33(1):116-28
pubmed: 23524583
Nature. 1969 Oct 11;224(5215):177-8
pubmed: 5343519
Nature. 2017 Jun 15;546(7658):431-435
pubmed: 28607484
Development. 1996 Mar;122(3):815-22
pubmed: 8631259
Science. 1947 Mar 14;105(2724):287-9
pubmed: 17835147