title: Mitotic Stress and Chromosomal Instability in Cancer: The Case for TPX2.
abstract: Cell cycle deregulation is a common motif in human cancer, and multiple therapeutic strategies are aimed to prevent tumor cell proliferation. Whereas most current therapies are designed to arrest cell cycle progression either in G1/S or in mitosis, new proposals include targeting the intrinsic chromosomal instability (CIN, an increased rate of gain or losses of chromosomes during cell division) or aneuploidy (a genomic composition that differs from diploid) that many tumor cells display. Why tumors cells are chromosomally unstable or aneuploid and what are the consequences of these alterations are not completely clear at present. Several mitotic regulators are overexpressed as a consequence of oncogenic alterations, and they are likely to alter the proper regulation of chromosome segregation in cancer cells. In this review, we propose the relevance of TPX2, a mitotic regulator involved in the formation of the mitotic spindle, in oncogene-induced mitotic stress. This protein, as well as its partner Aurora-A, is frequently overexpressed in human cancer, and its deregulation may participate not only in chromosome numeric aberrations but also in other forms of genomic instability in cancer cells.
authors: Cell Division and Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors: Ignacio
authors: I
authors: Pérez de Castro
authors: Marcos
authors: M
authors: Malumbres
keywords: TPX2; aurora kinases; cancer; chromosomal instability; mitosis; oncogene-induced mitotic stress
references: Mol Cancer Res. 2003 Feb;1(4):271-9
references: 12612055
references: J Biol Chem. 2009 Nov 27;284(48):33177-84
references: 19801554
references: Curr Biol. 2009 Nov 3;19(20):1712-7
references: 19818619
references: Nat Cell Biol. 2003 Mar;5(3):242-8
references: 12577065
references: Genes Dev. 2002 Sep 1;16(17):2274-85
references: 12208850
references: Cancer Res. 2012 Mar 15;72(6):1518-28
references: 22266221
references: PLoS One. 2012;7(6):e39801
references: 22761906
references: Curr Biol. 2002 Dec 10;12(23):2055-9
references: 12477396
references: PLoS One. 2010 Apr 08;5(4):e9983
references: 20386695
references: Cell Cycle. 2010 May;9(9):1711-6
references: 20404532
references: Biochim Biophys Acta. 2010 Dec;1806(2):230-9
references: 20708655
references: J Biol Chem. 2010 Jun 4;285(23):17628-35
references: 20335181
references: Nat Rev Cancer. 2009 Mar;9(3):153-66
references: 19238148
references: Int J Oncol. 2009 Jun;34(6):1565-71
references: 19424574
references: Science. 2007 May 25;316(5828):1160-6
references: 17525332
references: Genes Chromosomes Cancer. 2006 Oct;45(10):957-66
references: 16847944
references: Cell. 1997 Mar 7;88(5):593-602
references: 9054499
references: Curr Biol. 2003 Apr 15;13(8):691-7
references: 12699628
references: Carcinogenesis. 2007 May;28(5):899-912
references: 17259655
references: Oncol Rep. 2009 Feb;21(2):341-4
references: 19148505
references: Nature. 2009 Jul 9;460(7252):278-82
references: 19506557
references: EMBO J. 2011 Mar 2;30(5):906-19
references: 21297582
references: J Cell Biol. 1998 Nov 2;143(3):673-85
references: 9813089
references: J Biol Chem. 2008 Nov 14;283(46):31785-90
references: 18801727
references: Clin Cancer Res. 2007 Apr 1;13(7):2298-306
references: 17404115
references: Commun Integr Biol. 2011 Jul;4(4):409-12
references: 21966557
references: Mol Cell. 2003 Oct;12(4):851-62
references: 14580337
references: Genome Res. 2007 Nov;17(11):1550-61
references: 17908821
references: Mol Cell. 2009 Jul 31;35(2):228-39
references: 19647519
references: Nat Rev Cancer. 2002 Nov;2(11):815-25
references: 12415252
references: J Cell Biol. 2000 Jun 26;149(7):1405-18
references: 10871281
references: Curr Biol. 2009 Nov 3;19(20):1703-11
references: 19818618
references: Nat Cell Biol. 2008 Jul;10(7):858-65
references: 18536713
references: Front Biosci. 2005 Jan 01;10:728-42
references: 15569613
references: Dev Cell. 2005 Aug;9(2):237-48
references: 16054030
references: Curr Biol. 2008 Apr 8;18(7):519-25
references: 18372177
references: Cancer Cell. 2009 Dec 8;16(6):475-86
references: 19962666
references: Cell Signal. 2012 Aug;24(8):1677-89
references: 22560880
references: Cell. 2008 Feb 8;132(3):434-48
references: 18267074
references: EMBO J. 2012 May 2;31(9):2076-89
references: 22415365
references: PLoS One. 2012;7(1):e30890
references: 22303466
references: Science. 2008 Oct 31;322(5902):703-9
references: 18974345
references: Oncol Rep. 2012 May;27(5):1353-9
references: 22307108
references: Nat Cell Biol. 2008 Jul;10(7):802-11
references: 18552834
references: EMBO J. 2011 May 4;30(9):1690-704
references: 21441895
references: Gut. 2012 Nov;61(11):1568-75
references: 22207630
references: Clin Cancer Res. 2010 May 1;16(9):2518-28
references: 20388846
references: J Immunol. 2002 Jul 15;169(2):1102-9
references: 12097419
references: Strahlenther Onkol. 2005 Dec;181(12):755-61
references: 16362784
references: Cell Death Differ. 2012 Mar;19(3):369-77
references: 22223105
references: Brain Res. 2010 Sep 17;1352:200-7
references: 20599806
references: Nature. 2010 Feb 18;463(7283):899-905
references: 20164920
references: Mol Cell Biol. 2009 Feb;29(4):1059-71
references: 19075002
references: J Biol Chem. 2004 Mar 5;279(10):9008-15
references: 14701852
references: Cell Oncol. 2008;30(5):453
references: 18791276
references: Nat Rev Cancer. 2010 Feb;10(2):102-15
references: 20094045
references: Toxicology. 2008 Oct 30;252(1-3):49-55
references: 18723071
references: J Clin Oncol. 2003 May 1;21(9):1810-8
references: 12721258
references: Mol Biol Cell. 2008 Jul;19(7):2752-65
references: 18434591
references: J Cell Biol. 2008 Jul 28;182(2):289-300
references: 18663142
references: Cancer Cell. 2011 Jun 14;19(6):701-14
references: 21665145
references: Cell. 2001 Jan 12;104(1):83-93
references: 11163242
references: Cancer Lett. 2008 Apr 8;262(1):37-47
references: 18191020
references: PLoS One. 2011;6(11):e28120
references: 22140519
references: Cell Cycle. 2009 Aug;8(15):2413-9
references: 19556869
references: Anticancer Res. 2010 Sep;30(9):3541-7
references: 20944135
references: J Transl Med. 2008 Dec 11;6:79
references: 19077237
references: Cancer Res. 2005 Apr 1;65(7):2899-905
references: 15805292
references: Cancer Prev Res (Phila). 2009 Aug;2(8):702-11
references: 19638491
references: J Cell Biol. 2006 Jun 5;173(5):685-94
references: 16735579
references: Biochemistry. 2007 Sep 11;46(36):10287-95
references: 17705509
references: Arch Iran Med. 2007 Jan;10(1):27-31
references: 17198450
references: Science. 2008 Mar 7;319(5868):1352-5
references: 18323444
references: Curr Biol. 2006 Apr 18;16(8):743-54
references: 16631581
references: Arch Pathol Lab Med. 2008 Apr;132(4):694-7
references: 18384222
references: Curr Opin Cell Biol. 2009 Dec;21(6):796-805
references: 19836940
references: Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):3184-9
references: 22308418
references: Plant Cell. 2008 Oct;20(10):2783-97
references: 18941054
references: Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9625-30
references: 15983384
references: PLoS One. 2011 Feb 09;6(2):e16757
references: 21347367
references: Nat Cell Biol. 2009 Sep;11(9):1057-68
references: 19668197
references: Nat Genet. 2006 Sep;38(9):1043-8
references: 16921376
references: Mol Biol Cell. 2004 Dec;15(12):5318-28
references: 15385625
references: Cancer Cell. 2011 Jun 14;19(6):691-2
references: 21665141
references: PLoS One. 2012;7(9):e45431
references: 23029005
references: J Cell Sci. 2011 Jan 1;124(Pt 1):113-22
references: 21147853
references: Clin Cancer Res. 2006 Feb 15;12(4):1121-7
references: 16489064
references: Cancer Cell. 2007 Jan;11(1):9-23
references: 17189715
references: FEBS Lett. 1999 Dec 10;463(1-2):77-82
references: 10601642
references: Curr Biol. 2005 Dec 6;15(23):2156-63
references: 16332542
references: Nat Cell Biol. 2002 Nov;4(11):871-9
references: 12389033
references: Mol Biol Cell. 2008 May;19(5):2083-91
references: 18321990
references: Nature. 2001 Jan 18;409(6818):355-9
references: 11201745
references: Blood. 1997 Jul 1;90(1):226-33
references: 9207457
references: J Neuropathol Exp Neurol. 2011 Jan;70(1):1-12
references: 21157382
references: Clin Cancer Res. 2009 Nov 1;15(21):6519-28
references: 19861455
references: J Cell Sci. 2009 Mar 1;122(Pt 5):644-55
references: 19208764
references: J Cell Biol. 2002 Aug 19;158(4):617-23
references: 12177045
references: Curr Opin Pharmacol. 2008 Aug;8(4):375-83
references: 18644252
references: J Biol Chem. 2012 Dec 7;287(50):42206-22
references: 23045526
references: Eur J Haematol. 2005 Dec;75(6):498-504
references: 16313262
references: Cytogenet Cell Genet. 1999;84(3-4):182-3
references: 10393424
references: PLoS One. 2008 Oct 03;3(10):e3338
references: 18833336
references: Mol Cell Biol. 2005 Dec;25(23):10516-27
references: 16287863
references: Genes Chromosomes Cancer. 2008 Sep;47(9):755-65
references: 18506748
references: Curr Biol. 2006 Mar 7;16(5):536-41
references: 16527751
references: EMBO Rep. 2002 May;3(5):457-62
references: 11964384
references: Oncogene. 2008 Jul 3;27(29):4122-7
references: 18345035
references: Nat Rev Mol Cell Biol. 2007 May;8(5):379-93
references: 17426725