Skip to main content
SpringerLink
Log in

The spindle assembly checkpoint: perspectives in tumorigenesis and cancer therapy

  • Review
  • Published:
Frontiers in Biology

Abstract

Loss or gain of chromosomes, a condition known as aneuploidy, is a common feature of tumor cells and has therefore been proposed as the driving force for tumorigenesis. Such chromosomal instability can arise during mitosis as a result of mis-segregation of the duplicated sister chromatids to the two daughter cells. In normal cells, missegregation is usually prevented by the spindle assembly checkpoint (SAC), a sophisticated surveillance mechanism that inhibits mitotic exit until all chromosomes have successfully achieved bipolar attachment to spindle microtubules. Complete abrogation of SAC activity is lethal to normal as well as to tumor cells, as a consequence of massive chromosome mis-segregation. Importantly, many human aneuploid tumor cells exhibit a weakened SAC activity that allows them to tolerate gains or losses of a small number of chromosomes; and interfering with this SAC residual activity may constitute a suitable strategy to kill cancer cells. This review focuses on the potential link between SAC and tumorigenesis, and the therapeutic strategy to target the SAC for cancer treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aguilera A, Gómez-González B (2008). Genome instability: a mechanistic view of its causes and consequences. Nat Rev Genet, 9(3): 204–217

    Article  PubMed  CAS  Google Scholar 

  • Ando K, Kakeji Y, Kitao H, Iimori M, Zhao Y, Yoshida R, Oki E, Yoshinaga K, Matumoto T, Morita M, Sakaguchi Y, Maehara Y (2010). High expression of BUBR1 is one of the factors for inducing DNA aneuploidy and progression in gastric cancer. Cancer Sci, 101(3): 639–645

    Article  PubMed  CAS  Google Scholar 

  • Bagasra O, Prilliman K R (2004). RNA interference: the molecular immune system. J Mol Histol, 35(6): 545–553

    Article  PubMed  CAS  Google Scholar 

  • Bakhoum S F, Genovese G, Compton D A (2009). Deviant kinetochore microtubule dynamics underlie chromosomal instability. Curr Biol, 19(22): 1937–1942

    Article  PubMed  CAS  Google Scholar 

  • Bannon J H, Mc Gee M M (2009). Understanding the role of aneuploidy in tumorigenesis. Biochem Soc Trans, 37(Pt 4): 910–913

    Article  PubMed  CAS  Google Scholar 

  • Basu J, Bousbaa H, Logarinho E, Li Z, Williams B C, Lopes C, Sunkel C E, Goldberg M L (1999). Mutations in the essential spindle checkpoint gene bub1 cause chromosome missegregation and fail to block apoptosis in Drosophila. J Cell Biol, 146(1): 13–28

    Article  PubMed  CAS  Google Scholar 

  • Basu J, Logarinho E, Herrmann S, Bousbaa H, Li Z, Chan G K, Yen T J, Sunkel C E, Goldberg M L (1998). Localization of the Drosophila checkpoint control protein Bub3 to the kinetochore requires Bub1 but not Zw10 or Rod. Chromosoma, 107(6–7): 376–385

    Article  PubMed  CAS  Google Scholar 

  • Bharadwaj R, Yu H (2004). The spindle checkpoint, aneuploidy, and cancer. Oncogene, 23(11): 2016–2027

    Article  PubMed  CAS  Google Scholar 

  • Bolanos-Garcia VM (2009). Assessment of the mitotic spindle assembly checkpoint (SAC) as the target of anticancer therapies. Curr Cancer Drug Targets, 9(2): 131–141

    Article  PubMed  CAS  Google Scholar 

  • Burum-Auensen E, DeAngelis PM, Schjølberg A R, Røislien J, Mjåland O, Clausen O P (2008). Reduced level of the spindle checkpoint protein BUB1B is associated with aneuploidy in colorectal cancers. Cell Prolif, 41(4): 645–659

    Article  PubMed  CAS  Google Scholar 

  • Cahill D P, da Costa L T, Carson-Walter E B, Kinzler KW, Vogelstein B, Lengauer C (1999). Characterization of MAD2B and other mitotic spindle checkpoint genes. Genomics, 58(2): 181–187

    Article  PubMed  CAS  Google Scholar 

  • Cheeseman I M, Desai A (2008). Molecular architecture of the kinetochore-microtubule interface. Nat Rev Mol Cell Biol, 9(1):33–46

    Article  PubMed  CAS  Google Scholar 

  • Chi Y H, Jeang K T (2007). Aneuploidy and cancer. J Cell Biochem, 102(3): 531–538

    Article  PubMed  CAS  Google Scholar 

  • Clarke D J, Giménez-Abián J F (2000). Checkpoints controlling mitosis. Bioessays, 22(4): 351–363

    Article  PubMed  CAS  Google Scholar 

  • Dai W, Wang Q, Liu T, Swamy M, Fang Y, Xie S, Mahmood R, Yang Y M, Xu M, Rao C V (2004). Slippage of mitotic arrest and enhanced tumor development in mice with BubR1 haploinsufficiency. Cancer Res, 64(2): 440–445

    Article  PubMed  CAS  Google Scholar 

  • Dalton W B, Yang V W (2009). Role of prolonged mitotic checkpoint activation in the formation and treatment of cancer. Future Oncol, 5(9): 1363–1370

    Article  PubMed  CAS  Google Scholar 

  • Dobles M, Liberal V, Scott M L, Benezra R, Sorger P K (2000). Chromosome missegregation and apoptosis in mice lacking the mitotic checkpoint protein Mad2. Cell, 101(6): 635–645

    Article  PubMed  CAS  Google Scholar 

  • Earnshaw W C, Mackay A M (1994). Role of nonhistone proteins in the chromosomal events of mitosis. FASEB J, 8(12): 947–956

    PubMed  CAS  Google Scholar 

  • Fung M K, Cheung H W, Wong H L, Yuen H F, Ling M T, Chan K W, Wong Y C, Cheung A L, Wang X (2007). MAD2 expression and its significance in mitotic checkpoint control in testicular germ cell tumour. Biochim Biophys Acta, 1773(6): 821–832

    Article  PubMed  CAS  Google Scholar 

  • Ganem N J, Godinho S A, Pellman D (2009). A mechanism linking extra centrosomes to chromosomal instability. Nature, 460(7252): 278–282

    Article  PubMed  CAS  Google Scholar 

  • Gemma A, Hosoya Y, Seike M, Uematsu K, Kurimoto F, Hibino S, Yoshimura A, Shibuya M, Kudoh S, Emi M (2001). Genomic structure of the human MAD2 gene and mutation analysis in human lung and breast cancers. Lung Cancer, 32(3): 289–295

    Article  PubMed  CAS  Google Scholar 

  • Gemma A, Seike M, Seike Y, Uematsu K, Hibino S, Kurimoto F, Yoshimura A, Shibuya M, Harris C C, Kudoh S (2000). Somatic mutation of the hBUB1 mitotic checkpoint gene in primary lung cancer. Genes Chromosomes Cancer, 29(3): 213–218

    Article  PubMed  CAS  Google Scholar 

  • Grabsch H I, Askham J M, Morrison E E, Pomjanski N, Lickvers K, Parsons W J, Boecking A, Gabbert H E, Mueller W (2004). Expression of BUB1 protein in gastric cancer correlates with the histological subtype, but not with DNA ploidy or microsatellite instability. J Pathol, 202(2): 208–214

    Article  PubMed  CAS  Google Scholar 

  • Green R A, Kaplan K B (2003). Chromosome instability in colorectal tumor cells is associated with defects in microtubule plus-end attachments caused by a dominant mutation in APC. J Cell Biol, 163(5): 949–961

    Article  PubMed  CAS  Google Scholar 

  • Haruki N, Saito H, Harano T, Nomoto S, Takahashi T, Osada H, Fujii Y, Takahashi T (2001). Molecular analysis of the mitotic checkpoint genes BUB1, BUBR1 and BUB3 in human lung cancers. Cancer Lett, 162(2): 201–205

    Article  PubMed  CAS  Google Scholar 

  • Hernando E, Orlow I, Liberal V, Nohales G, Benezra R, Cordon-Cardo C (2001). Molecular analyses of the mitotic checkpoint components hsMAD2, hBUB1 and hBUB3 in human cancer. Int J Cancer, 95(4): 223–227

    Article  PubMed  CAS  Google Scholar 

  • Howell B J, McEwen B F, Canman J C, Hoffman D B, Farrar E M, Rieder C L, Salmon E D (2001). Cytoplasmic dynein/dynactin drives kinetochore protein transport to the spindle poles and has a role in mitotic spindle checkpoint inactivation. J Cell Biol, 155(7): 1159–1172

    Article  PubMed  CAS  Google Scholar 

  • Hoyt M A, Totis L, Roberts B T (1991). S. cerevisiae genes required for cell cycle arrest in response to loss of microtubule function. Cell, 66(3): 507–517

    CAS  Google Scholar 

  • Imai Y, Shiratori Y, Kato N, Inoue T, Omata M (1999). Mutational inactivation of mitotic checkpoint genes, hsMAD2 and hBUB1, is rare in sporadic digestive tract cancers. Jpn J Cancer Res, 90(8): 837–840

    PubMed  CAS  Google Scholar 

  • Jeganathan K, Malureanu L, Baker D J, Abraham S C, van Deursen J M (2007). Bub1 mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis. J Cell Biol, 179(2): 255–267

    Article  PubMed  CAS  Google Scholar 

  • Ji A M, Su D, Che O, Li W S, Sun L, Zhang Z Y, Yang B, Xu F (2009). Functional gene silencing mediated by chitosan/siRNA nanocomplexes. Nanotechnology, 20(40): 405103

    Article  PubMed  CAS  Google Scholar 

  • Jordan M A, Wilson L (2004). Microtubules as a target for anticancer drugs. Nat Rev Cancer, 4(4): 253–265

    Article  PubMed  CAS  Google Scholar 

  • Kalitsis P, Fowler K J, Griffiths B, Earle E, Chow CW, Jamsen K, Choo K H (2005). Increased chromosome instability but not cancer predisposition in haploinsufficient Bub3 mice. Genes Chromosomes Cancer, 44(1): 29–36

    Article  PubMed  CAS  Google Scholar 

  • Kienitz A, Vogel C, Morales I, Müller R, Bastians H (2005). Partial downregulation of MAD1 causes spindle checkpoint inactivation and aneuploidy, but does not confer resistance towards taxol. Oncogene, 24(26): 4301–4310

    Article  PubMed  CAS  Google Scholar 

  • Ko Y H, Roh J H, Son Y I, Chung M K, Jang J Y, Byun H, Baek C H, Jeong H S (2010). Expression of mitotic checkpoint proteins BUB1B and MAD2L1 in salivary duct carcinomas. J Oral Pathol Med, 39(4): 349–355

    Article  PubMed  Google Scholar 

  • Kops G J (2009). Dividing the goods: co-ordination of chromosome biorientation and mitotic checkpoint signalling by mitotic kinases. Biochem Soc Trans, 37(Pt 5): 971–975

    Article  PubMed  CAS  Google Scholar 

  • Kops G J, Foltz D R, Cleveland D W (2004). Lethality to human cancercells through massive chromosome loss by inhibition of the mitotic checkpoint. Proc Natl Acad Sci USA, 101(23): 8699–8704

    Article  PubMed  CAS  Google Scholar 

  • Kops G J, Weaver B A, Cleveland D W (2005). On the road to cancer: aneuploidy and the mitotic checkpoint. Nat Rev Cancer, 5(10): 773–785

    Article  PubMed  CAS  Google Scholar 

  • Lin S F, Lin P M, Yang M C, Liu T C, Chang J G, Sue Y C, Chen T P (2002). Expression of hBUB1 in acute myeloid leukemia. Leuk Lymphoma, 43(2): 385–391

    Article  PubMed  CAS  Google Scholar 

  • Logarinho E, Bousbaa H (2008). Kinetochore-microtubule interactions “in check” by Bub1, Bub3 and BubR1: The dual task of attaching and signalling. Cell Cycle, 7(12): 1763–176

    Article  PubMed  CAS  Google Scholar 

  • Masuda A, Maeno K, Nakagawa T, Saito H, Takahashi T (2003). Association between mitotic spindle checkpoint impairment and susceptibility to the induction of apoptosis by anti-microtubule agents in human lung cancers. Am J Pathol, 163(3): 1109–1116

    Article  PubMed  CAS  Google Scholar 

  • Michel L, Diaz-Rodriguez E, Narayan G, Hernando E, Murty V V, Benezra R (2004). Complete loss of the tumor suppressor MAD2 causes premature cyclin B degradation and mitotic failure in human somatic cells. Proc Natl Acad Sci USA, 101(13): 4459–4464

    Article  PubMed  CAS  Google Scholar 

  • Mimori K, Inoue H, Alder H, Ueo H, Tanaka Y, Mori M (2001). Mutation analysis of hBUB1, human mitotic checkpoint gene in multiple carcinomas. Oncol Rep, 8(1): 39–42

    PubMed  CAS  Google Scholar 

  • Minhas K M, Singh B, Jiang W W, Sidransky D, Califano J A (2003). Spindle assembly checkpoint defects and chromosomal instability in head and neck squamous cell carcinoma. Int J Cancer, 107(1): 46–52

    Article  PubMed  CAS  Google Scholar 

  • Mondal G, Sengupta S, Panda C K, Gollin S M, Saunders W S, Roychoudhury S (2007). Overexpression of Cdc20 leads to impairment of the spindle assembly checkpoint and aneuploidization in oral cancer. Carcinogenesis, 28(1): 81–92

    Article  PubMed  CAS  Google Scholar 

  • Morgan D O (1999). Regulation of the APC and the exit from mitosis. Nat Cell Biol, 1(2): E47–E53

    Article  PubMed  CAS  Google Scholar 

  • Musacchio A, Salmon E D (2007). The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol, 8(5): 379–393

    Article  PubMed  CAS  Google Scholar 

  • Myrie K A, Percy M J, Azim J N, Neeley C K, Petty E M (2000). Mutation and expression analysis of human BUB1 and BUB1B in aneuploid breast cancer cell lines. Cancer Lett, 152(2): 193–199

    Article  PubMed  CAS  Google Scholar 

  • Nasmyth K (2005). How do so few control so many? Cell, 120(6): 739–746

    Article  PubMed  CAS  Google Scholar 

  • Niikura Y, Dixit A, Scott R, Perkins G, Kitagawa K (2007). BUB1 mediation of caspase-independent mitotic death determines cell fate. J Cell Biol, 178(2): 283–296

    Article  PubMed  CAS  Google Scholar 

  • Ohshima K, Haraoka S, Yoshioka S, Hamasaki M, Fujiki T, Suzumiya J, Kawasaki C, Kanda M, Kikuchi M (2000). Mutation analysis of mitotic checkpoint genes (hBUB1 and hBUBR1) and microsatellite instability in adult T-cell leukemia/lymphoma. Cancer Lett, 158(2): 141–150

    Article  PubMed  CAS  Google Scholar 

  • Olesen S H, Thykjaer T, Ørntoft T F (2001). Mitotic checkpoint genes hBUB1, hBUB1B, hBUB3 and TTK in human bladder cancer, screening for mutations and loss of heterozygosity. Carcinogenesis, 22(5): 813–815

    Article  PubMed  CAS  Google Scholar 

  • Orr B, Bousbaa H, Sunkel C E (2007). Mad2-independent spindle assembly checkpoint activation and controlled metaphase-anaphase transition in Drosophila S2 cells. Mol Biol Cell, 18(3): 850–863

    Article  PubMed  CAS  Google Scholar 

  • Ouyang B, Knauf J A, Ain K, Nacev B, Fagin J A (2002). Mechanisms of aneuploidy in thyroid cancer cell lines and tissues: evidence for mitotic checkpoint dysfunction without mutations in BUB1 and BUBR1. Clin Endocrinol (Oxf), 56(3): 341–350

    Article  CAS  Google Scholar 

  • Pan C, Yan M, Yao J, Xu J, Long Z, Huang H, Liu Q (2008). Aurora kinase small molecule inhibitor destroys mitotic spindle, suppresses cell growth, and induces apoptosis in oral squamous cancer cells. Oral Oncol, 44(7): 639–645

    Article  PubMed  CAS  Google Scholar 

  • Percy M J, Myrie K A, Neeley C K, Azim J N, Ethier S P, Petty E M (2000). Expression and mutational analyses of the human MAD2L1 gene in breast cancer cells. Genes Chromosomes Cancer, 29(4): 356–362

    Article  PubMed  CAS  Google Scholar 

  • Pinto M, Soares M J, Cerveira N, Henrique R, Ribeiro F R, Oliveira J, Jerónimo C, Teixeira M R (2007). Expression changes of the MAD mitotic checkpoint gene family in renal cell carcinomas characterized by numerical chromosome changes. Virchows Arch, 450(4): 379–385

    Article  PubMed  CAS  Google Scholar 

  • Pinto M, Vieira J, Ribeiro F R, Soares M J, Henrique R, Oliveira J, Jerónimo C, Teixeira M R (2008). Overexpression of the mitotic checkpoint genes BUB1 and BUBR1 is associated with genomic complexity in clear cell kidney carcinomas. Cell Oncol, 30(5): 389–395

    PubMed  CAS  Google Scholar 

  • Przewloka M R, Glover D M (2009). The kinetochore and the centromere: a working long distance relationship. Annu Rev Genet, 43(1): 439–465

    Article  PubMed  CAS  Google Scholar 

  • Reddy S K, Rape M, Margansky W A, Kirschner M W (2007). Ubiquitination by the anaphase-promoting complex drives spindle checkpoint inactivation. Nature, 446(7138): 921–925

    Article  PubMed  CAS  Google Scholar 

  • Reis R M, Nakamura M, Masuoka J, Watanabe T, Colella S, Yonekawa Y, Kleihues P, Ohgaki H (2001). Mutation analysis of hBUB1, hBUBR1 and hBUB3 genes in glioblastomas. Acta Neuropathol, 101(4): 297–304

    PubMed  CAS  Google Scholar 

  • Rimkus C, Friederichs J, Rosenberg R, Holzmann B, Siewert J R, Janssen K P (2007). Expression of the mitotic checkpoint gene MAD2L2 has prognostic significance in colon cancer. Int J Cancer, 120(1): 207–211

    Article  PubMed  CAS  Google Scholar 

  • Roberts B T, Farr K A, Hoyt MA (1994). The Saccharomyces cerevisiae checkpoint gene BUB1 encodes a novel protein kinase. Mol Cell Biol, 14(12): 8282–8291

    PubMed  CAS  Google Scholar 

  • Saeki A, Tamura S, Ito N, Kiso S, Matsuda Y, Yabuuchi I, Kawata S, Matsuzawa Y (2002). Frequent impairment of the spindle assembly checkpoint in hepatocellular carcinoma. Cancer, 94(7): 2047–2054

    Article  PubMed  CAS  Google Scholar 

  • Satchi-Fainaro R, Duncan R (2006) Advances in Polymer Science Polymer Therapeutics I: Springer.

  • Sato M, Sekido Y, Horio Y, Takahashi M, Saito H, Minna J D, Shimokata K, Hasegawa Y (2000). Infrequent mutation of the hBUB1 and hBUBR1 genes in human lung cancer. Jpn J Cancer Res, 91(5): 504–509

    PubMed  CAS  Google Scholar 

  • Scannevin R H, Wang K, Jow F, Megules J, Kopsco D C, Edris W, Carroll K C, Lü Q, Xu W, Xu Z, Katz A H, Olland S, Lin L, Taylor M, Stahl M, Malakian K, Somers W, Mosyak L, Bowlby M R, Chanda P, Rhodes K J (2004). Two N-terminal domains of Kv4 K(+) channels regulate binding to and modulation by KChIP1. Neuron, 41(4): 587–598

    Article  PubMed  CAS  Google Scholar 

  • Schafer K A (1998). The cell cycle: a review. Vet Pathol, 35(6): 461–478

    Article  PubMed  CAS  Google Scholar 

  • Schmidt M, Medema R H (2006). Exploiting the compromised spindle assembly checkpoint function of tumor cells: dawn on the horizon? Cell Cycle, 5(2): 159–163

    Article  PubMed  CAS  Google Scholar 

  • Screpanti E, Santaguida S, Nguyen T, Silvestri R, Gussio R, Musacchio A, Hamel E, DeWulf P (2010). A screen for kinetochore-microtubule interaction inhibitors identifies novel antitubulin compounds. PLoS ONE, 5(7): e11603

    Article  PubMed  Google Scholar 

  • Seike M, Gemma A, Hosoya Y, Hosomi Y, Okano T, Kurimoto F, Uematsu K, Takenaka K, Yoshimura A, Shibuya M, Ui-Tei K, Kudoh S (2002). The promoter region of the human BUBR1 gene and its expression analysis in lung cancer. Lung Cancer, 38(3): 229–234

    Article  PubMed  Google Scholar 

  • Shi Q, Hu M, Luo M, Liu Q, Jiang F, Zhang Y, Wang S, Yan C, Weng Y (2010) Reduced expression of Mad2 and Bub1 proteins is associated with spontaneous abortions. Mol Hum Reprod

  • Shigeishi H, Oue N, Kuniyasu H, Wakikawa A, Yokozaki H, Ishikawa T, Yasui W (2001a). Expression of Bub1 gene correlates with tumor proliferating activity in human gastric carcinomas. Pathobiology, 69(1): 24–29

    Article  PubMed  CAS  Google Scholar 

  • Shigeishi H, Yokozaki H, Kuniyasu H, Nakagawa H, Ishikawa T, Tahara E, Yasui W (2001b). No mutations of the Bub1 gene in human gastric carcinomas. Oncol Rep, 8(4): 791–794

    PubMed  CAS  Google Scholar 

  • Silkworth W T, Nardi I K, Scholl L M, Cimini D (2009). Multipolar spindle pole coalescence is a major source of kinetochore misattachment and chromosome mis-segregation in cancer cells. PLoS ONE, 4(8): e6564

    Article  PubMed  Google Scholar 

  • Stegmeier F, Rape M, Draviam V M, Nalepa G, Sowa M E, Ang X L, McDonald E R 3rd, Li M Z, Hannon G J, Sorger P K, Kirschner M W, Harper J W, Elledge S J (2007). Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities. Nature, 446(7138): 876–881

    Article  PubMed  CAS  Google Scholar 

  • Sudakin V, Chan G K, Yen T J (2001). Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2. J Cell Biol, 154(5): 925–936

    Article  PubMed  CAS  Google Scholar 

  • Suijkerbuijk S J, Kops G J (2008). Preventing aneuploidy: the contribution of mitotic checkpoint proteins. Biochim Biophys Acta, 1786(1): 24–31

    PubMed  CAS  Google Scholar 

  • Sze K M, Ching Y P, Jin D Y, Ng I O (2004). Association of MAD2 expression with mitotic checkpoint competence in hepatoma cells. J Biomed Sci, 11(6): 920–927

    Article  PubMed  CAS  Google Scholar 

  • Takahashi T, Haruki N, Nomoto S, Masuda A, Saji S, Osada H, Takahashi T (1999). Identification of frequent impairment of the mitotic checkpoint and molecular analysis of the mitotic checkpoint genes, hsMAD2 and p55CDC, in human lung cancers. Oncogene, 18(30): 4295–4300

    Article  PubMed  CAS  Google Scholar 

  • Tanaka K, Mohri Y, Ohi M, Yokoe T, Koike Y, Morimoto Y, Miki C, Tonouchi H, Kusunoki M (2008). Mitotic checkpoint genes, hsMAD2 and BubR1, in oesophageal squamous cancer cells and their association with 5-fluorouracil and cisplatin-based radiochemotherapy. Clin Oncol (R Coll Radiol), 20(8): 639–646

    CAS  Google Scholar 

  • Tsukasaki K, Miller C W, Greenspun E, Eshaghian S, Kawabata H, Fujimoto T, Tomonaga M, Sawyers C, Said JW, Koeffler H P (2001). Mutations in the mitotic check point gene, MAD1L1, in human cancers. Oncogene, 20(25): 3301–3305

    Article  PubMed  CAS  Google Scholar 

  • Tyson J J, Novak B (2008). Temporal organization of the cell cycle. Curr Biol, 18(17): R759–R768

    Article  PubMed  CAS  Google Scholar 

  • Wada N, Yoshida A, Miyagi Y, Yamamoto T, Nakayama H, Suganuma N, Matsuzu K, Masudo K, Hirakawa S, Rino Y, Masuda M, Imada T (2008). Overexpression of the mitotic spindle assembly checkpoint genes hBUB1, hBUBR1 and hMAD2 in thyroid carcinomas with aggressive nature. Anticancer Res, 28(1A): 139–144

    PubMed  CAS  Google Scholar 

  • Wang L, Yin F, Du Y, Chen B, Liang S, Zhang Y, Du W, Wu K, Ding J, Fan D (2010). Depression of MAD2 inhibits apoptosis and increases proliferation and multidrug resistance in gastric cancer cells by regulating the activation of phosphorylated survivin. Tumour Biol, 31(3): 225–232

    Article  PubMed  CAS  Google Scholar 

  • Wang Z M, Lin H K, Zhu S R, Liu T F, Zhou Z F, Chen Y T (2000). Synthesis, characterization and cytotoxicity of lanthanum(III) complexes with novel 1,10-phenanthroline-2,9-bis-alpha-amino acid conjugates. Anticancer Drug Des, 15(6): 405–411

    PubMed  CAS  Google Scholar 

  • Weaver B A, Silk A D, Montagna C, Verdier-Pinard P, Cleveland D W (2007). Aneuploidy acts both oncogenically and as a tumor suppressor. Cancer Cell, 11(1): 25–36

    Article  PubMed  CAS  Google Scholar 

  • Weitzel D H, Vandré D D (2000). Differential spindle assembly checkpoint response in human lung adenocarcinoma cells. Cell Tissue Res, 300(1): 57–65

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi K, Okami K, Hibi K, Wehage S L, Jen J, Sidransky D (1999). Mutation analysis of hBUB1 in aneuploid HNSCC and lung cancer cell lines. Cancer Lett, 139(2): 183–187

    Article  PubMed  CAS  Google Scholar 

  • Yoon D S, Wersto R P, Zhou W, Chrest F J, Garrett E S, Kwon T K, Gabrielson E (2002). Variable levels of chromosomal instability and mitotic spindle checkpoint defects in breast cancer. Am J Pathol, 161(2): 391–397

    Article  PubMed  Google Scholar 

  • Zeng X, Sigoillot F, Gaur S, Choi S, Pfaff K L, Oh D C, Hathaway N, Dimova N, Cuny G D, King R W (2010). Pharmacologic inhibition of the anaphase-promoting complex induces a spindle checkpoint-dependent mitotic arrest in the absence of spindle damage. Cancer Cell, 18(4): 382–395

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centro de Investigação em Ciências da Saúde (CICS), Instituto Superior de Ciências da Saúde-Norte, CESPU, Rua Central de Gandra, 1317, 4585-116, Gandra PRD, Portugal

    Joana Barbosa, Ana Vanessa Nascimento, Juliana Faria, Patrícia Silva & Hassan Bousbaa

Authors
  1. Joana Barbosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ana Vanessa Nascimento
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Juliana Faria
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Patrícia Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hassan Bousbaa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hassan Bousbaa.

Additional information

These authors contributed equally to this work

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barbosa, J., Nascimento, A.V., Faria, J. et al. The spindle assembly checkpoint: perspectives in tumorigenesis and cancer therapy. Front. Biol. 6, 147–155 (2011). https://doi.org/10.1007/s11515-011-1122-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11515-011-1122-x

Keywords

Search

Navigation