Mechanisms of aneuploidy and its suppression by tumour suppressor proteins

Swiss Medical Weekly

Volumn 141, Issue MARCH, 2011, Pages

  Thoma, Claudio R ^a   Toso, Alberto ^a,b   Meraldi, Patrick ^a   Krek, Wilhelm ^a  

^a ETH ZURICH   (Switzerland)

^b REGIONAL HOSPITAL OF LUGANO   (Switzerland)

Author keywords

Aneuploidy; Tumour suppressor proteins; Whole chromosomal instability

Indexed keywords

APC PROTEIN; CYCLIN DEPENDENT KINASE; HYPOXIA INDUCIBLE FACTOR; PROTEIN E7; PROTEIN MAD2; PROTEIN P53; REPRESSOR ELEMENT 1 SILENCING TRANSCRIPTION FACTOR; RETINOBLASTOMA PROTEIN; TUMOR SUPPRESSOR PROTEIN; UNCLASSIFIED DRUG; VON HIPPEL LINDAU PROTEIN; RE1 SILENCING TRANSCRIPTION FACTOR; RE1-SILENCING TRANSCRIPTION FACTOR; REPRESSOR PROTEIN;

ANEUPLOIDY; CANCER CELL; CANCER INHIBITION; CELL CYCLE G2 PHASE; CHROMOSOMAL INSTABILITY; COLON CANCER; DISEASE MODEL; DNA REPLICATION; GENE MUTATION; GENETIC TRANSCRIPTION; HUMAN; LUNG SMALL CELL CANCER; NEUROBLASTOMA; NONHUMAN; PROTEIN BINDING; PROTEIN EXPRESSION; REVIEW; WHOLE CHROMOSOME INSTABILITY; GENE; GENETICS; METABOLISM; NEOPLASM;

ADENOMATOUS POLYPOSIS COLI PROTEIN; ANEUPLOIDY; CHROMOSOMAL INSTABILITY; GENES, CDC; HUMANS; NEOPLASMS; REPRESSOR PROTEINS; RETINOBLASTOMA PROTEIN; TUMOR SUPPRESSOR PROTEIN P53; TUMOR SUPPRESSOR PROTEINS; VON HIPPEL-LINDAU TUMOR SUPPRESSOR PROTEIN;

EID: 79955659666     PISSN: 14247860     EISSN: None     Source Type: Journal    
DOI: 10.4414/smw.2011.13170     Document Type: Review

References (98)

1. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57-70. (Pubitemid 30046295)
2. Kroemer G, Pouyssegur J. Tumor cell metabolism: cancer's Achilles' heel. Cancer Cell. 2008;13:472-82. (Pubitemid 351766797)
3. Luo J, Solimini NL, Elledge SJ. Principles of cancer therapy: oncogene and non-oncogene addiction. Cell. 2009;136:823-37.
4. Hahn WC, Weinberg RA. Modelling the molecular circuitry of cancer. Nat Rev Cancer. 2002;2:331-41. (Pubitemid 37328946)
5. COSMIC. (2009) Catalog of somatic mutations in cancer. http://www.sanger.ac.uk/genetics/CGP/cosmic/.
6. Boveri T. Zur Frage der Entstehung maligner Tumoren. Gustav Fischer, Jena, 1914.
7. Mitelman F, Johansson B, Mertens F. (2010) Mitelman Database of Chromosome Aberrations in Cancer. http://cgap.nci.nih.gov/Chromosomes/Mitelman.
8. Duesberg P, Li R. Multistep carcinogenesis: a chain reaction of aneuploidizations. Cell Cycle. 2003;2:202-10.
9. Zimonjic D, Brooks MW, Popescu N, Weinberg RA, Hahn WC. Derivation of human tumor cells in vitro without widespread genomic instability. Cancer Res. 2001;61:8838-44. (Pubitemid 34013898)
10. Weaver BA, Silk AD, Montagna C, Verdier-Pinard P, Cleveland DW. Aneuploidy acts both oncogenically and as a tumor suppressor. Cancer Cell. 2007;11:25-36. (Pubitemid 46070223)
11. Gasparini P, Sozzi G, Pierotti MA. The role of chromosomal alterations in human cancer development. J Cell Biochem. 2007;102:320-31. (Pubitemid 47519406)
12. Rowley JD. Identificaton of a translocation with quinacrine fluorescence in a patient with acute leukemia. Ann Genet. 1973;16:109-12.
13. Sandberg AA, Meloni-Ehrig AM. Cytogenetics and genetics of human cancer: methods and accomplishments. Cancer Genet Cytogenet. 2010;203:102-26.
14. Lingle WL, Lukasiewicz K, Salisbury JL. Deregulation of the centrosome cycle and the origin of chromosomal instability in cancer. Adv Exp Med Biol. 2005;570:393-421. (Pubitemid 47413181)
15. Cimini D, Wan X, Hirel CB, Salmon ED. Aurora kinase promotes turnover of kinetochore microtubules to reduce chromosome segregation errors. Curr Biol. 2006;16:1711-8.
16. Knowlton AL, Lan W, Stukenberg PT. Aurora B is enriched at merotelic attachment sites, where it regulates MCAK. Curr Biol. 2006;16:1705-10. (Pubitemid 44691788)
17. Cimini D. Detection and correction of merotelic kinetochore orientation by Aurora B and its partners. Cell Cycle. 2007;6:1558-64. (Pubitemid 47327940)
18. Musacchio A, Salmon ED. The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol. 2007;8:379-93.
19. Cheeseman IM, Desai A. Molecular architecture of the kinetochore- microtubule interface. Nat Rev Mol Cell Biol. 2008;9:33-46.
20. Rieder CL, Cole RW, Khodjakov A, Sluder G. The checkpoint delaying anaphase in response to chromosome monoorientation is mediated by an inhibitory signal produced by unattached kinetochores. J Cell Biol. 1995;130:941-8.
21. Sironi L, Mapelli M, Knapp S, De Antoni A, Jeang KT, Musacchio A. Crystal structure of the tetrameric Mad1-Mad2 core complex: implications of a "safety belt" binding mechanism for the spindle checkpoint. Embo J. 2002;21:2496-506.
22. Chan GK, Jablonski SA, Sudakin V, Hittle JC, Yen TJ. Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E functions at kinetochores and binds the cyclosome/APC. J Cell Biol. 1999;146:941-54. (Pubitemid 29430438)
23. Yao X, Abrieu A, Zheng Y, Sullivan KF, Cleveland DW. CENP-E forms a link between attachment of spindle microtubules to kinetochores and the mitotic checkpoint. Nat Cell Biol. 2000;2:484-91.
24. Johnson VL, Scott MI, Holt SV, Hussein D, Taylor SS. Bub1 is required for kinetochore localization of BubR1, Cenp-E, Cenp-F and Mad2, and chromosome congression. J Cell Sci. 2004;117:1577-89. (Pubitemid 38559832)
25. Meraldi P, Sorger PK. A dual role for Bub1 in the spindle checkpoint and chromosome congression. Embo J. 2005;24:1621-33. (Pubitemid 40646451)
26. De Antoni A, Pearson CG, Cimini D, Canman JC, Sala V, Nezi L, et al. The Mad1/Mad2 complex as a template for Mad2 activation in the spindle assembly checkpoint. Curr Biol. 2005;15:214-25.
27. Mapelli M, Massimiliano L, Santaguida S, Musacchio A. The Mad2 conformational dimer: structure and implications for the spindle assembly checkpoint. Cell. 2007;131:730-43. (Pubitemid 350087197)
28. Luo X, Fang G, Coldiron M, Lin Y, Yu H, Kirschner MW, Wagner G. Structure of the Mad2 spindle assembly checkpoint protein and its interaction with Cdc20. Nat Struct Biol. 2000;7:224-9. (Pubitemid 30140769)
29. Kim Y, Heuser JE, Waterman CM, Cleveland DW. CENP-E combines a slow, processive motor and a flexible coiled coil to produce an essential motile kinetochore tether. J Cell Biol. 2008;181:411-9. (Pubitemid 351645031)
30. Mao Y, Abrieu A, Cleveland DW. Activating and silencing the mitotic checkpoint through CENP-E-dependent activation/inactivation of BubR1. Cell. 2003;114:87-98. (Pubitemid 36859843)
31. Howell BJ, McEwen BF, Canman JC, Hoffman DB, Farrar EM, Rieder CL, Salmon ED. Cytoplasmic dynein/dynactin drives kinetochore protein transport to the spindle poles and has a role in mitotic spindle checkpoint inactivation. J Cell Biol. 2001;155:1159-72.
32. Wojcik E, Basto R, Serr M, Scaerou F, Karess R, Hays T. Kinetochore dynein: its dynamics and role in the transport of the Rough deal checkpoint protein. Nat Cell Biol. 2001;3;1001-7. (Pubitemid 34428745)
33. Michel LS, Liberal V, Chatterjee A, Kirchwegger R, Pasche B, Gerald W, et al. MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells. Nature. 2001;409:355-9. (Pubitemid 32151241)
34. Sotillo R, Hernando E, Diaz-Rodriguez E, Teruya-Feldstein J, Cordon-Cardo C, Lowe SW, Benezra R. Mad2 overexpression promotes aneuploidy and tumorigenesis in mice. Cancer Cell. 2007;11:9-23. (Pubitemid 46054519)
35. Cahill DP, Lengauer C, Yu J, Riggins GJ, Willson JK, Markowitz SD, et al. Mutations of mitotic checkpoint genes in human cancers. Nature. 1998;392:300-3. (Pubitemid 28155105)
36. Weaver BA, Cleveland DW. Does aneuploidy cause cancer? Curr Opin Cell Biol. 2006;18:658-67.
37. Dobles M, Liberal V, Scott ML, Benezra R, Sorger PK. Chromosome missegregation and apoptosis in mice lacking the mitotic checkpoint protein Mad2. Cell. 2000;101:635-45.
38. Iwanaga Y, Chi YH, Miyazato A, Sheleg S, Haller K, Peloponese JM Jr, et al. Heterozygous deletion of mitotic arrestdeficient protein 1 (MAD1) increases the incidence of tumors in mice. Cancer Res. 2007;67:160-6. (Pubitemid 46142771)
39. Jeganathan K, Malureanu L, Baker DJ, Abraham SC, van Deursen JM. Bub1 mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis. J Cell Biol. 2007;179:255-67. (Pubitemid 350004890)
40. Kalitsis P, Earle E, Fowler KJ, Choo KH. Bub3 gene disruption in mice reveals essential mitotic spindle checkpoint function during early embryogenesis. Genes Dev. 2000;1:2277-82.
41. Wang Q, Liu T, Fang Y, Xie S, Huang X, Mahmood R, et al. BUBR1 deficiency results in abnormal megakaryopoiesis. Blood. 2004;103:1278-85. (Pubitemid 38168638)
42. Weaver BA, Bonday ZQ, Putkey FR, Kops GJ, Silk AD, Cleveland DW. Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss. J Cell Biol. 2003;162:551-63. (Pubitemid 37022934)
43. Perez de Castro I, de Carcer G, Malumbres M. A census of mitotic cancer genes: new insights into tumor cell biology and cancer therapy. Carcinogenesis. 2007;28:899-912. (Pubitemid 47072171)
44. Kalitsis P, Fowler KJ, Griffiths B, Earle E, Chow CW, Jamsen K, Choo KH. Increased chromosome instability but not cancer predisposition in haploinsufficient Bub3 mice. Genes Chromosomes Cancer. 2005;44:29-36. (Pubitemid 41060194)
45. Baker DJ, Jeganathan KB, Cameron JD, Thompson M, Juneja S, Kopecka A, et al. BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice. Nat Genet. 2004;36:744-9. (Pubitemid 38886637)
46. Dai W, Wang Q, Liu T, Swamy M, Fang Y, Xie S, Mahmood R, et al. Slippage of mitotic arrest and enhanced tumor development in mice with BubR1 haploinsufficiency. Cancer Res. 2004;64:440-5. (Pubitemid 38120879)
47. Babu JR, Jeganathan KB, Baker DJ, Wu X, Kang-Decker N, van Deursen JM. Rae1 is an essential mitotic checkpoint regulator that cooperates with Bub3 to prevent chromosome missegregation. J Cell Biol. 2003;160:341-53. (Pubitemid 36182725)
48. Foijer F, Draviam VM, Sorger PK. Studying chromosome instability in the mouse. Biochim Biophys Acta. 2008;1786:73-82.
49. Schvartzman JM, Sotillo R, Benezra R. Mitotic chromosomal instability and cancer: mouse modelling of the human disease. Nat Rev Cancer. 10:102-15.
50. Segal DJ, McCoy EE. Studies on Down's syndrome in tissue culture. I. Growth rates and protein contents of fibroblast cultures. J Cell Physiol. 1974;83:85-90.
51. Torres EM, Sokolsky T, Tucker CM, Chan LY, Boselli M, Dunham MJ, Amon A. Effects of aneuploidy on cellular physiology and cell division in haploid yeast. Science. 2007;317:916-24. (Pubitemid 47301313)
52. Williams BR, Prabhu VR, Hunter KE, Glazier CM, Whittaker CA, Housman DE, Amon A. Aneuploidy affects proliferation and spontaneous immortalization in mammalian cells. Science. 2008;322:703-9.
53. Williams BR, Amon A. Aneuploidy: cancer's fatal flaw? Cancer Res. 2009;69:5289-91.
54. Nicholson JM, Duesberg P. On the karyotypic origin and evolution of cancer cells. Cancer Genet Cytogenet. 2009;194:96-110.
55. Torres EM, Dephoure N, Panneerselvam A, Tucker CM, Whittaker CA, Gygi SP, et al. Identification of aneuploidytolerating mutations. Cell. 2010;143:71-83.
56. Sotillo R, Schvartzman JM, Socci ND, Benezra R. Mad2-induced chromosome instability leads to lung tumour relapse after oncogene withdrawal. Nature.
57. Kinzler KW, Vogelstein B. Lessons from hereditary colorectal cancer. Cell. 1996;87:159-70. (Pubitemid 26358996)
58. Clevers H. Wnt/beta-catenin signaling in development and disease. Cell. 2006;127:469-80.
59. Nathke IS. The adenomatous polyposis coli protein: the Achilles heel of the gut epithelium. Annu Rev Cell Dev Biol. 2004;20:337-66. (Pubitemid 39488642)
60. Mimori-Kiyosue Y, Shiina N, Tsukita S. Adenomatous polyposis coli (APC) protein moves along microtubules and concentrates at their growing ends in epithelial cells. J Cell Biol. 2000;148:505-18.
61. Nathke IS, Adams CL, Polakis P, Sellin JH, Nelson WJ. The adenomatous polyposis coli tumor suppressor protein localizes to plasma membrane sites involved in active cell migration. J Cell Biol. 1996;134:165-79. (Pubitemid 26231528)
62. Fodde R, Kuipers J, Rosenberg C, Smits R, Kielman M, Gaspar C, et al. Mutations in the APC tumour suppressor gene cause chromosomal instability. Nat Cell Biol. 2001;3:433-8. (Pubitemid 32288454)
63. Kaplan KB, Burds AA, Swedlow JR, Bekir SS, Sorger PK, Nathke IS. A role for the Adenomatous Polyposis Coli protein in chromosome segregation. Nat Cell Biol. 2001;3:429-32. (Pubitemid 32288453)
64. Dikovskaya D, Schiffmann D, Newton IP, Oakley A, Kroboth K, Sansom O, et al. Loss of APC induces polyploidy as a result of a combination of defects in mitosis and apoptosis. J Cell Biol. 2007;176:183-95. (Pubitemid 46143259)
65. Zhang J, Ahmad S, Mao Y. BubR1 and APC/EB1 cooperate to maintain metaphase chromosome alignment. J Cell Biol. 2007;178:773-84. (Pubitemid 47347363)
66. Negrini S, Gorgoulis VG, Halazonetis TD. Genomic instability - an evolving hallmark of cancer. Nat Rev Mol Cell Biol. 2010;11:220-8.
67. Fukasawa K, Choi T, Kuriyama R, Rulong S, Vande Woude GF. Abnormal centrosome amplification in the absence of p53. Science. 1996;271:1744-7. (Pubitemid 26102826)
68. Oikawa T, Okuda M, Ma Z, Goorha R, Tsujimoto H, Inokuma H, Fukasawa K. Transcriptional control of BubR1 by p53 and suppression of centrosome amplification by BubR1. Mol Cell Biol. 2005;25:4046-61. (Pubitemid 40617653)
69. Sabado Alvarez C. Molecular biology of retinoblastoma. Clin Transl Oncol. 2008;10:389-94.
70. Chen HZ, Tsai SY, Leone G. Emerging roles of E2Fs in cancer: an exit from cell cycle control. Nat Rev Cancer. 2009;9:785-97.
71. Meraldi P, Lukas J, Fry AM, Bartek J, Nigg EA. Centrosome duplication in mammalian somatic cells requires E2F and Cdk2-cyclin A. Nat Cell Biol. 1999;1:88-93. (Pubitemid 129501949)
72. Lentini L, Pipitone L, Di Leonardo A. Functional inactivation of pRB results in aneuploid mammalian cells after release from a mitotic block. Neoplasia. 2002;4:380-7. (Pubitemid 34976953)
73. Zheng L, Flesken-Nikitin A, Chen PL, Lee WH. Deficiency of Retinoblastoma gene in mouse embryonic stem cells leads to genetic instability. Cancer Res. 2002;62:2498-502. (Pubitemid 34462725)
74. Hernando E, Nahle Z, Juan G, Diaz-Rodriguez E, Alaminos M, Hemann M, et al. Rb inactivation promotes genomic instability by uncoupling cell cycle progression from mitotic control. Nature. 2004;430:797-802. (Pubitemid 39071352)
75. Coschi CH, Martens AL, Ritchie K, Francis SM, Chakrabarti S, Berube NG, Dick FA. Mitotic chromosome condensation mediated by the retinoblastoma protein is tumor-suppressive. Genes Dev. 2010;24:1351-63.
76. Manning AL, Longworth MS, Dyson NJ. Loss of pRB causes centromere dysfunction and chromosomal instability. Genes Dev. 2010;24:1364-76.
77. van Harn T, Foijer F, van Vugt M, Banerjee R, Yang F, Oostra A, et al. Loss of Rb proteins causes genomic instability in the absence of mitogenic signaling. Genes Dev. 2010;24:1377-88.
78. Westbrook TF, Martin ES, Schlabach MR, Leng Y, Liang AC, Feng B, et al. A genetic screen for candidate tumor suppressors identifies REST. Cell. 2005;121:837-48. (Pubitemid 40806416)
79. Coulson JM, Edgson JL, Woll PJ, Quinn JP. A splice variant of the neuron-restrictive silencer factor repressor is expressed in small cell lung cancer: a potential role in derepression of neuroendocrine genes and a useful clinical marker. Cancer Res. 2000;60:1840-4. (Pubitemid 30207641)
80. Palm K, Metsis M, Timmusk T. Neuron-specific splicing of zinc finger transcription factor REST/NRSF/XBR is frequent in neuroblastomas and conserved in human, mouse and rat. Brain Res Mol Brain Res. 1999;72:30-9. (Pubitemid 29474912)
81. Guardavaccaro D, Frescas D, Dorrello NV, Peschiaroli A, Multani AS, Cardozo T, et al. Control of chromosome stability by the beta-TrCP-REST-Mad2 axis. Nature. 2008;452:365-9. (Pubitemid 351430786)
82. Westbrook TF, Hu G, Ang XL, Mulligan P, Pavlova NN, Liang A, et al. SCFbeta-TRCP controls oncogenic transformation and neural differentiation through REST degradation. Nature. 2008;452:370-4. (Pubitemid 351430796)
83. Frew IJ, Krek W. pVHL: a multipurpose adaptor protein. Sci Signal, 1, pe30. (2008).
84. Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME, et al. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature. 1999;399:271-5. (Pubitemid 29246458)
85. Hergovich A, Lisztwan J, Barry R, Ballschmieter P, Krek W. Regulation of microtubule stability by the von Hippel- Lindau tumour suppressor protein pVHL. Nat Cell Biol. 2003;5:64-70. (Pubitemid 36054331)
86. Thoma CR, Matov A, Gutbrodt KL, Hoerner CR, Smole Z, Krek W, Danuser G. Quantitative image analysis identifies pVHL as a key regulator of microtubule dynamic instability. J Cell Biol. 2010;190:991-1003.
87. Schermer B, Ghenoiu C, Bartram M, Muller RU, Kotsis F, Hohne M, et al. The von Hippel-Lindau tumor suppressor protein controls ciliogenesis by orienting microtubule growth. J Cell Biol. 2006;175:547-54. (Pubitemid 44790608)
88. Thoma CR, Frew IJ, Hoerner CR, Montani M, Moch H, Krek W. pVHL and GSK3beta are components of a primary cilium-maintenance signalling network. Nat Cell Biol. 2007;9:588-95. (Pubitemid 46696541)
89. Ohh M, Yauch RL, Lonergan KM, Whaley JM, Stemmer-Rachamimov AO, Louis DN, et al. The von Hippel-Lindau tumor suppressor protein is required for proper assembly of an extracellular fibronectin matrix. Mol Cell. 1998;1:959-68. (Pubitemid 128379257)
90. Thoma CR, Toso A, Gutbrodt KL, Reggi SP, Frew IJ, Schraml P, et al. VHL loss causes spindle misorientation and chromosome instability. Nat Cell Biol. 2009;11:994-1001.
91. Draviam VM, Shapiro I, Aldridge B, Sorger PK. Misorientation and reduced stretching of aligned sister kinetochores promote chromosome missegregation in EB1- or APC-depleted cells. Embo J. 2006;25:2814-27. (Pubitemid 43980388)
92. Klaus A, Birchmeier W. Wnt signalling and its impact on development and cancer. Nat Rev Cancer. 2008;8:387-98. (Pubitemid 351589714)
93. Nathke I. Relationship between the role of the adenomatous polyposis coli protein in colon cancer and its contribution to cytoskeletal regulation. Biochem Soc Trans. 2005;33:694-7. (Pubitemid 41160841)
94. Meek DW. Tumour suppression by p53: a role for the DNA damage response? Nat Rev Cancer. 2009;9:714-23.
95. Zuckerman V. Wolyniec K, Sionov RV, Haupt S, Haupt Y. Tumour suppression by p53: the importance of apoptosis and cellular senescence. J Pathol. 2009;219:3-15.
96. Thompson SL, Compton DA. Proliferation of aneuploid human cells is limited by a p53-dependent mechanism. J Cell Biol. 2010;188;369-81.
97. Burkhart DL, Sage J. Cellular mechanisms of tumour suppression by the retinoblastoma gene. Nat Rev Cancer. 2008;8:671-82.
98. Kaelin WG, Jr. The von Hippel-Lindau tumour suppressor protein: O2 sensing and cancer. Nat Rev Cancer. 2008;8:865-73.