Skip to main content
SpringerLink
Log in

The Kinetochore-Cancer Connection

  • Chapter
  • First Online:
The Kinetochore:

Abstract

An abnormal chromosome number and gross structural aberrations of chromosomes are hallmarks of human cancers. These chromosomal changes are thought to occur due to the accelerated rate of gains or losses of whole or large portions of chromosomes, termed chromosomal instability (CIN), as the result of continuous chromosome missegregation during mitosis. Recently, the mechanism of proper mitotic processes has been unraveled and the aberrant function of factors involved in equal chromosome segregation has been reported in various cancers. Among them, the centromere and kinetochore have a pivotal role in ensuring accurate chromosome segregation; thus, defects in kinetochore function are candidate sources of CIN and the generation of aneuploidy. In this chapter, recent progress in our understanding of how kinetochore dysfunction underlies CIN is introduced and described. Furthermore, I will discuss how it leads to the development of cancer.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adams, R.R., Eckley, D.M., Vagnarelli, P., Wheatley, S.P., Gerloff, D.L., Mackay, A.M., Svingen, P.A., Kaufmann, S.H., and Earnshaw, W.C. (2001). Human INCENP colocalizes with the Aurora-B/AIRK2 kinase on chromosomes and is overexpressed in tumour cells. Chromosoma 110, 65–74.

    PubMed  CAS  Google Scholar 

  • Adams, R.R., Wheatley, S.P., Gouldsworthy, A.M., Kandels-Lewis, S.E., Carmena, M., Smythe, C., Gerloff, D.L., and Earnshaw, W.C. (2000). INCENP binds the Aurora-related kinase AIRK2 and is required to target it to chromosomes, the central spindle and cleavage furrow. Curr Biol 10, 1075–1078.

    PubMed  CAS  Google Scholar 

  • Ambrosini, G., Adida, C., and Altieri, D.C. (1997). A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 3, 917–921.

    PubMed  CAS  Google Scholar 

  • Andreassen, P.R., Lohez, O.D., Lacroix, F.B., and Margolis, R.L. (2001). Tetraploid state induces p53-dependent arrest of nontransformed mammalian cells in G1. Mol Biol Cell 12, 1315–1328.

    PubMed  CAS  Google Scholar 

  • Aoki, K., Aoki, M., Sugai, M., Harada, N., Miyoshi, H., Tsukamoto, T., Mizoshita, T., Tatematsu, M., Seno, H., Chiba, T., Oshima, M., Hsieh, C.L., and Taketo, M.M. (2007). Chromosomal instability by beta-catenin/TCF transcription in APC or beta-catenin mutant cells. Oncogene 26, 3511–3520.

    PubMed  CAS  Google Scholar 

  • Araki, K., Nozaki, K., Ueba, T., Tatsuka, M., and Hashimoto, N. (2004). High expression of Aurora-B/Aurora and Ipll-like midbody-associated protein (AIM-1) in astrocytomas. J Neurooncol 67, 53–64.

    PubMed  Google Scholar 

  • Armes, J.E., Hammet, F., de Silva, M., Ciciulla, J., Ramus, S.J., Soo, W.K., Mahoney, A., Yarovaya, N., Henderson, M.A., Gish, K., Hutchins, A.M., Price, G.R., and Venter, D.J. (2004). Candidate tumor-suppressor genes on chromosome arm 8p in early-onset and high-grade breast cancers. Oncogene 23, 5697–5702.

    PubMed  CAS  Google Scholar 

  • Auer, G.U., Caspersson, T.O., and Wallgren, A.S. (1980). DNA content and survival in mammary carcinoma. Anal Quant Cytol 2, 161–165.

    PubMed  CAS  Google Scholar 

  • Babu, J.R., Jeganathan, K.B., Baker, D.J., Wu, X., Kang-Decker, N., and van Deursen, J.M. (2003). Rae1 is an essential mitotic checkpoint regulator that cooperates with Bub3 to prevent chromosome missegregation. J Cell Biol 160, 341–353.

    PubMed  CAS  Google Scholar 

  • Banks, J.D., and Heald, R. (2004). Adenomatous polyposis coli associates with the microtubule-destabilizing protein XMCAK. Curr Biol 14, 2033–2038.

    PubMed  CAS  Google Scholar 

  • Bao, L., Kimzey, A., Sauter, G., Sowadski, J.M., Lu, K.P., and Wang, D.G. (2004). Prevalent overexpression of prolyl isomerase Pin1 in human cancers. Am J Pathol 164, 1727–1737.

    PubMed  CAS  Google Scholar 

  • Bischoff, J.R., Anderson, L., Zhu, Y., Mossie, K., Ng, L., Souza, B., Schryver, B., Flanagan, P., Clairvoyant, F., Ginther, C., Chan, C.S., Novotny, M., Slamon, D.J., and Plowman, G.D. (1998). A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. Embo J 17, 3052–3065.

    PubMed  CAS  Google Scholar 

  • Bishop, J.M. (1987). The molecular genetics of cancer. Science 235, 305–311.

    PubMed  CAS  Google Scholar 

  • Cahill, D.P., Lengauer, C., Yu, J., Riggins, G.J., Willson, J.K., Markowitz, S.D., Kinzler, K.W., and Vogelstein, B. (1998). Mutations of mitotic checkpoint genes in human cancers. Nature 392, 300–303.

    PubMed  CAS  Google Scholar 

  • Carter, S.L., Eklund, A.C., Kohane, I.S., Harris, L.N., and Szallasi, Z. (2006). A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers. Nat Genet 38, 1043–1048.

    PubMed  CAS  Google Scholar 

  • Chang, H., Yeung, J., Xu, W., Ning, Y., and Patterson, B. (2006a). Significant increase of CKS1B amplification from monoclonal gammopathy of undetermined significance to multiple myeloma and plasma cell leukaemia as demonstrated by interphase fluorescence in situ hybridisation. Br J Haematol 134, 613–615.

    Google Scholar 

  • Chang, J.L., Chen, T.H., Wang, C.F., Chiang, Y.H., Huang, Y.L., Wong, F.H., Chou, C.K., and Chen, C.M. (2006b). Borealin/Dasra B is a cell cycle-regulated chromosomal passenger protein and its nuclear accumulation is linked to poor prognosis for human gastric cancer. Exp Cell Res 312, 962–973.

    Google Scholar 

  • Charrasse, S., Mazel, M., Taviaux, S., Berta, P., Chow, T., and Larroque, C. (1995). Characterization of the cDNA and pattern of expression of a new gene over-expressed in human hepatomas and colonic tumors. Eur J Biochem 234, 406–413.

    PubMed  CAS  Google Scholar 

  • Chieffi, P., Cozzolino, L., Kisslinger, A., Libertini, S., Staibano, S., Mansueto, G., De Rosa, G., Villacci, A., Vitale, M., Linardopoulos, S., Portella, G., and Tramontano, D. (2006). Aurora B expression directly correlates with prostate cancer malignancy and influence prostate cell proliferation. Prostate 66, 326–333.

    PubMed  CAS  Google Scholar 

  • Chieffi, P., Troncone, G., Caleo, A., Libertini, S., Linardopoulos, S., Tramontano, D., and Portella, G. (2004). Aurora B expression in normal testis and seminomas. J Endocrinol 181, 263–270.

    PubMed  CAS  Google Scholar 

  • Clark, G.M., Allred, D.C., Hilsenbeck, S.G., Chamness, G.C., Osborne, C.K., Jones, D., and Lee, W.H. (1997). Mitosin (a new proliferation marker) correlates with clinical outcome in node-negative breast cancer. Cancer Res 57, 5505–5508.

    PubMed  CAS  Google Scholar 

  • Cleveland, D.W., Mao, Y., and Sullivan, K.F. (2003). Centromeres and kinetochores: from epigenetics to mitotic checkpoint signaling. Cell 112, 407–421.

    PubMed  CAS  Google Scholar 

  • Cooke, C.A., Heck, M.M., and Earnshaw, W.C. (1987). The inner centromere protein (INCENP) antigens: movement from inner centromere to midbody during mitosis. J Cell Biol 105, 2053–2067.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • de la Guardia, C., Casiano, C.A., Trinidad-Pinedo, J., and Baez, A. (2001). CENP-F gene amplification and overexpression in head and neck squamous cell carcinomas. Head Neck 23, 104–112.

    PubMed  Google Scholar 

  • Dikovskaya, D., Schiffmann, D., Newton, I.P., Oakley, A., Kroboth, K., Sansom, O., Jamieson, T.J., Meniel, V., Clarke, A., and Nathke, I.S. (2007). Loss of APC induces polyploidy as a result of a combination of defects in mitosis and apoptosis. J Cell Biol 176, 183–195.

    PubMed  CAS  Google Scholar 

  • Duesberg, P., and Li, R. (2003). Multistep carcinogenesis: a chain reaction of aneuploidizations. Cell Cycle 2, 202–210.

    PubMed  CAS  Google Scholar 

  • Duesberg, P., Rausch, C., Rasnick, D., and Hehlmann, R. (1998). Genetic instability of cancer cells is proportional to their degree of aneuploidy. Proc Natl Acad Sci USA 95, 13692–13697.

    PubMed  CAS  Google Scholar 

  • Eckerdt, F., Yuan, J., and Strebhardt, K. (2005). Polo-like kinases and oncogenesis. Oncogene 24, 267–276.

    PubMed  CAS  Google Scholar 

  • Erlanson, M., Casiano, C.A., Tan, E.M., Lindh, J., Roos, G., and Landberg, G. (1999). Immunohistochemical analysis of the proliferation associated nuclear antigen CENP-F in non-Hodgkin's lymphoma. Mod Pathol 12, 69–74.

    PubMed  CAS  Google Scholar 

  • Esguerra, R.L., Jia, L., Kaneko, T., Sakamoto, K., Okada, N., and Takagi, M. (2004). Immunohistochemical analysis of centromere protein F expression in buccal and gingival squamous cell carcinoma. Pathol Int 54, 82–89.

    PubMed  CAS  Google Scholar 

  • Fodde, R., Kuipers, J., Rosenberg, C., Smits, R., Kielman, M., Gaspar, C., van Es, J.H., Breukel, C., Wiegant, J., Giles, R.H., and Clevers, H. (2001). Mutations in the APC tumour suppressor gene cause chromosomal instability. Nat Cell Biol 3, 433–438.

    PubMed  CAS  Google Scholar 

  • Fujii, T., Nomoto, S., Koshikawa, K., Yatabe, Y., Teshigawara, O., Mori, T., Inoue, S., Takeda, S., and Nakao, A. (2006). Overexpression of pituitary tumor transforming gene 1 in HCC is associated with angiogenesis and poor prognosis. Hepatology 43, 1267–1275.

    PubMed  CAS  Google Scholar 

  • Fujiwara, T., Bandi, M., Nitta, M., Ivanova, E.V., Bronson, R.T., and Pellman, D. (2005). Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells. Nature 437, 1043–1047.

    PubMed  CAS  Google Scholar 

  • Galipeau, P.C., Cowan, D.S., Sanchez, C.A., Barrett, M.T., Emond, M.J., Levine, D.S., Rabinovitch, P.S., and Reid, B.J. (1996). 17p (p53) allelic losses, 4 N (G2/tetraploid) populations, and progression to aneuploidy in Barrett's esophagus. Proc Natl Acad Sci USA 93, 7081–7084.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Genkai, N., Homma, J., Sano, M., Tanaka, R., and Yamanaka, R. (2006). Increased expression of pituitary tumor-transforming gene (PTTG)-1 is correlated with poor prognosis in glioma patients. Oncol Rep 15, 1569–1574.

    PubMed  CAS  Google Scholar 

  • Giannini, G., Ambrosini, M.I., Di Marcotullio, L., Cerignoli, F., Zani, M., MacKay, A.R., Screpanti, I., Frati, L., and Gulino, A. (2003). EGF- and cell-cycle-regulated STAG1/PMEPA1/ERG1.2 belongs to a conserved gene family and is overexpressed and amplified in breast and ovarian cancer. Mol Carcinog 38, 188–200.

    PubMed  CAS  Google Scholar 

  • Grabsch, H., Takeno, S., Parsons, W.J., Pomjanski, N., Boecking, A., Gabbert, H.E., and Mueller, W. (2003). Overexpression of the mitotic checkpoint genes BUB1, BUBR1, and BUB3 in gastric cancer--association with tumour cell proliferation. J Pathol 200, 16–22.

    PubMed  CAS  Google Scholar 

  • Green, R.A., and 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, 949–961.

    PubMed  CAS  Google Scholar 

  • Gritsko, T.M., Coppola, D., Paciga, J.E., Yang, L., Sun, M., Shelley, S.A., Fiorica, J.V., Nicosia, S.V., and Cheng, J.Q. (2003). Activation and overexpression of centrosome kinase BTAK/Aurora-A in human ovarian cancer. Clin Cancer Res 9, 1420–1426.

    PubMed  CAS  Google Scholar 

  • Grutzmann, R., Pilarsky, C., Ammerpohl, O., Luttges, J., Bohme, A., Sipos, B., Foerder, M., Alldinger, I., Jahnke, B., Schackert, H.K., Kalthoff, H., Kremer, B., Kloppel, G., and Saeger, H.D. (2004). Gene expression profiling of microdissected pancreatic ductal carcinomas using high-density DNA microarrays. Neoplasia 6, 611–622.

    PubMed  Google Scholar 

  • Gurzov, E.N., and Izquierdo, M. (2006). RNA interference against Hec1 inhibits tumor growth in vivo. Gene Ther 13, 1–7.

    PubMed  CAS  Google Scholar 

  • Hadjihannas, M.V., Bruckner, M., Jerchow, B., Birchmeier, W., Dietmaier, W., and Behrens, J. (2006). Aberrant Wnt/beta-catenin signaling can induce chromosomal instability in colon cancer. Proc Natl Acad Sci USA 103, 10747–10752.

    PubMed  CAS  Google Scholar 

  • Han, S., Park, K., Kim, H.Y., Lee, M.S., Kim, H.J., Kim, Y.D., Yuh, Y.J., Kim, S.R., and Suh, H.S. (2000). Clinical implication of altered expression of Mad1 protein in human breast carcinoma. Cancer 88, 1623–1632.

    PubMed  CAS  Google Scholar 

  • Hanks, S., Coleman, K., Reid, S., Plaja, A., Firth, H., Fitzpatrick, D., Kidd, A., Mehes, K., Nash, R., Robin, N., Shannon, N., Tolmie, J., Swansbury, J., Irrthum, A., Douglas, J., and Rahman, N. (2004). Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Nat Genet 36, 1159–1161.

    PubMed  CAS  Google Scholar 

  • Hansemann, D. (1890). Ueber asymmetrische Zelltheilung in Epithelkrebsen und deren biologische Bedeutung. Virschown Arch Pathol Anat 119, 299–326.

    PubMed  CAS  Google Scholar 

  • Harrington, E.A., Bebbington, D., Moore, J., Rasmussen, R.K., Ajose-Adeogun, A.O., Nakayama, T., Graham, J.A., Demur, C., Hercend, T., Diu-Hercend, A., Su, M., Golec, J.M., and Miller, K.M. (2004). VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat Med 10, 262–267.

    PubMed  CAS  Google Scholar 

  • Hartwell, L., Weinert, T., Kadyk, L., and Garvik, B. (1994). Cell cycle checkpoints, genomic integrity, and cancer. Cold Spring Harb Symp Quant Biol 59, 259–263.

    PubMed  CAS  Google Scholar 

  • Hartwell, L.H., Szankasi, P., Roberts, C.J., Murray, A.W., and Friend, S.H. (1997). Integrating genetic approaches into the discovery of anticancer drugs. Science 278, 1064–1068.

    PubMed  CAS  Google Scholar 

  • Hayama, S., Daigo, Y., Kato, T., Ishikawa, N., Yamabuki, T., Miyamoto, M., Ito, T., Tsuchiya, E., Kondo, S., and Nakamura, Y. (2006). Activation of CDCA1-KNTC2, members of centromere protein complex, involved in pulmonary carcinogenesis. Cancer Res 66, 10339–10348.

    PubMed  CAS  Google Scholar 

  • Hayette, S., Tigaud, I., Vanier, A., Martel, S., Corbo, L., Charrin, C., Beillard, E., Deleage, G., Magaud, J.P., and Rimokh, R. (2000). AF15q14, a novel partner gene fused to the MLL gene in an acute myeloid leukaemia with a t(11;15)(q23;q14). Oncogene 19, 4446–4450.

    PubMed  CAS  Google Scholar 

  • Hayward, D.G., Clarke, R.B., Faragher, A.J., Pillai, M.R., Hagan, I.M., and Fry, A.M. (2004). The centrosomal kinase Nek2 displays elevated levels of protein expression in human breast cancer. Cancer Res 64, 7370–7376.

    PubMed  CAS  Google Scholar 

  • Heaney, A.P., Singson, R., McCabe, C.J., Nelson, V., Nakashima, M., and Melmed, S. (2000). Expression of pituitary-tumour transforming gene in colorectal tumours. Lancet 355, 716–719.

    PubMed  CAS  Google Scholar 

  • Hempen, P.M., Kurpad, H., Calhoun, E.S., Abraham, S., and Kern, S.E. (2003). A double missense variation of the BUB1 gene and a defective mitotic spindle checkpoint in the pancreatic cancer cell line Hs766T. Hum Mutat 21, 445.

    PubMed  Google Scholar 

  • Hernando, E., Nahle, Z., Juan, G., Diaz-Rodriguez, E., Alaminos, M., Hemann, M., Michel, L., Mittal, V., Gerald, W., Benezra, R., Lowe, S.W., and Cordon-Cardo, C. (2004). Rb inactivation promotes genomic instability by uncoupling cell cycle progression from mitotic control. Nature 430, 797–802.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Heun, P., Erhardt, S., Blower, M.D., Weiss, S., Skora, A.D., and Karpen, G.H. (2006). Mislocalization of the Drosophila centromere-specific histone CID promotes formation of functional ectopic kinetochores. Dev Cell 10, 303–315.

    PubMed  CAS  Google Scholar 

  • Holtrich, U., Wolf, G., Brauninger, A., Karn, T., Bohme, B., Rubsamen-Waigmann, H., and Strebhardt, K. (1994). Induction and down-regulation of PLK, a human serine/threonine kinase expressed in proliferating cells and tumors. Proc Natl Acad Sci USA 91, 1736–1740.

    PubMed  CAS  Google Scholar 

  • Hsu, J.Y., Sun, Z.W., Li, X., Reuben, M., Tatchell, K., Bishop, D.K., Grushcow, J.M., Brame, C.J., Caldwell, J.A., Hunt, D.F., Lin, R., Smith, M.M., and Allis, C.D. (2000). Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and nematodes. Cell 102, 279–291.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Jiang, Z., Li, X., Hu, J., Zhou, W., Jiang, Y., Li, G., and Lu, D. (2006). Promoter hypermethylation-mediated down-regulation of LATS1 and LATS2 in human astrocytoma. Neurosci Res 56, 450–458.

    PubMed  CAS  Google Scholar 

  • Jimenez-Velasco, A., Roman-Gomez, J., Agirre, X., Barrios, M., Navarro, G., Vazquez, I., Prosper, F., Torres, A., and Heiniger, A. (2005). Downregulation of the large tumor suppressor 2 (LATS2/KPM) gene is associated with poor prognosis in acute lymphoblastic leukemia. Leukemia 19, 2347–2350.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Kaitna, S., Pasierbek, P., Jantsch, M., Loidl, J., and Glotzer, M. (2002). The aurora B kinase AIR-2 regulates kinetochores during mitosis and is required for separation of homologous Chromosomes during meiosis. Curr Biol 12, 798–812.

    PubMed  CAS  Google Scholar 

  • Kallakury, B.V., Sheehan, C.E., Ambros, R.A., Fisher, H.A., Kaufman, R.P., Jr., and Ross, J.S. (1997). The prognostic significance of p34cdc2 and cyclin D1 protein expression in prostate adenocarcinoma. Cancer 80, 753–763.

    PubMed  CAS  Google Scholar 

  • Kallio, M.J., McCleland, M.L., Stukenberg, P.T., and Gorbsky, G.J. (2002). Inhibition of aurora B kinase blocks chromosome segregation, overrides the spindle checkpoint, and perturbs microtubule dynamics in mitosis. Curr Biol 12, 900–905.

    PubMed  CAS  Google Scholar 

  • Kaplan, K.B., Burds, A.A., Swedlow, J.R., Bekir, S.S., Sorger, P.K., and Nathke, I.S. (2001). A role for the Adenomatous Polyposis Coli protein in chromosome segregation. Nat Cell Biol 3, 429–432.

    PubMed  CAS  Google Scholar 

  • Katayama, H., Ota, T., Jisaki, F., Ueda, Y., Tanaka, T., Odashima, S., Suzuki, F., Terada, Y., and Tatsuka, M. (1999). Mitotic kinase expression and colorectal cancer progression. J Natl Cancer Inst 91, 1160–1162.

    PubMed  CAS  Google Scholar 

  • Kawakami, K., Enokida, H., Tachiwada, T., Gotanda, T., Tsuneyoshi, K., Kubo, H., Nishiyama, K., Takiguchi, M., Nakagawa, M., and Seki, N. (2006). Identification of differentially expressed genes in human bladder cancer through genome-wide gene expression profiling. Oncol Rep 16, 521–531.

    PubMed  CAS  Google Scholar 

  • Keen, N., and Taylor, S. (2004). Aurora-kinase inhibitors as anticancer agents. Nat Rev Cancer 4, 927–936.

    PubMed  CAS  Google Scholar 

  • Kettunen, E., Anttila, S., Seppanen, J.K., Karjalainen, A., Edgren, H., Lindstrom, I., Salovaara, R., Nissen, A.M., Salo, J., Mattson, K., Hollmen, J., Knuutila, S., and Wikman, H. (2004). Differentially expressed genes in nonsmall cell lung cancer: expression profiling of cancer-related genes in squamous cell lung cancer. Cancer Genet Cytogenet 149, 98–106.

    PubMed  CAS  Google Scholar 

  • Kim, H.S., Park, K.H., Kim, S.A., Wen, J., Park, S.W., Park, B., Gham, C.W., Hyung, W.J., Noh, S.H., Kim, H.K., and Song, S.Y. (2005a). Frequent mutations of human Mad2, but not Bub1, in gastric cancers cause defective mitotic spindle checkpoint. Mutat Res 578, 187–201.

    Google Scholar 

  • Kim, J.M., Sohn, H.Y., Yoon, S.Y., Oh, J.H., Yang, J.O., Kim, J.H., Song, K.S., Rho, S.M., Yoo, H.S., Kim, Y.S., Kim, J.G., and Kim, N.S. (2005b). Identification of gastric cancer-related genes using a cDNA microarray containing novel expressed sequence tags expressed in gastric cancer cells. Clin Cancer Res 11, 473–482.

    Google Scholar 

  • Kinzler, K.W., and Vogelstein, B. (1996). Lessons from hereditary colorectal cancer. Cell 87, 159–170.

    PubMed  CAS  Google Scholar 

  • Kirchner, S., Stopper, H., Papp, T., Eckert, I., Yoo, H.J., Vig, B.K., and Schiffmann, D. (1993). Cytogenetic changes in primary, immortal`d and malignant mammalian cells. Toxicol Lett 67, 283–295.

    PubMed  CAS  Google Scholar 

  • Kirschner-Schwabe, R., Lottaz, C., Todling, J., Rhein, P., Karawajew, L., Eckert, C., von Stackelberg, A., Ungethum, U., Kostka, D., Kulozik, A.E., Ludwig, W.D., Henze, G., Spang, R., Hagemeier, C., and Seeger, K. (2006). Expression of late cell cycle genes and an increased proliferative capacity characterize very early relapse of childhood acute lymphoblastic leukemia. Clin Cancer Res 12, 4553–4561.

    PubMed  CAS  Google Scholar 

  • Kiyomitsu, T., Obuse, C., and Yanagida, M. (2007). Human Blinkin/AF15q14 is required for chromosome alignment and the mitotic checkpoint through direct interaction with Bub1 and BubR1. Dev Cell 13, 663–676.

    PubMed  CAS  Google Scholar 

  • Koon, N., Schneider-Stock, R., Sarlomo-Rikala, M., Lasota, J., Smolkin, M., Petroni, G., Zaika, A., Boltze, C., Meyer, F., Andersson, L., Knuutila, S., Miettinen, M., and El-Rifai, W. (2004). Molecular targets for tumour progression in gastrointestinal stromal tumours. Gut 53, 235–240.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Kronenwett, U., Huwendiek, S., Ostring, C., Portwood, N., Roblick, U.J., Pawitan, Y., Alaiya, A., Sennerstam, R., Zetterberg, A., and Auer, G. (2004). Improved grading of breast adenocarcinomas based on genomic instability. Cancer Res 64, 904–909.

    PubMed  CAS  Google Scholar 

  • Kunitoku, N., Sasayama, T., Marumoto, T., Zhang, D., Honda, S., Kobayashi, O., Hatakeyama, K., Ushio, Y., Saya, H., and Hirota, T. (2003). CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B at inner centromeres and for kinetochore function. Dev Cell 5, 853–864.

    PubMed  CAS  Google Scholar 

  • Lengauer, C., Kinzler, K.W., and Vogelstein, B. (1997). Genetic instability in colorectal cancers. Nature 386, 623–627.

    PubMed  CAS  Google Scholar 

  • Lengauer, C., Kinzler, K.W., and Vogelstein, B. (1998). Genetic instabilities in human cancers. Nature 396, 643–649.

    PubMed  CAS  Google Scholar 

  • Leupin, N., Kuhn, A., Hugli, B., Grob, T.J., Jaggi, R., Tobler, A., Delorenzi, M., and Fey, M.F. (2006). Gene expression profiling reveals consistent differences between clinical samples of human leukaemias and their model cell lines. Br J Haematol 135, 520–523.

    PubMed  CAS  Google Scholar 

  • Levine, D.S., Sanchez, C.A., Rabinovitch, P.S., and Reid, B.J. (1991). Formation of the tetraploid intermediate is associated with the development of cells with more than four centrioles in the elastase-simian virus 40 tumor antigen transgenic mouse model of pancreatic cancer. Proc Natl Acad Sci USA 88, 6427–6431.

    PubMed  CAS  Google Scholar 

  • Li, D., Zhu, J., Firozi, P.F., Abbruzzese, J.L., Evans, D.B., Cleary, K., Friess, H., and Sen, S. (2003). Overexpression of oncogenic STK15/BTAK/Aurora A kinase in human pancreatic cancer. Clin Cancer Res 9, 991–997.

    PubMed  CAS  Google Scholar 

  • Li, F. (2005). Role of survivin and its splice variants in tumorigenesis. Br J Cancer 92, 212–216.

    PubMed  CAS  Google Scholar 

  • Li, M., Lin, Y.M., Hasegawa, S., Shimokawa, T., Murata, K., Kameyama, M., Ishikawa, O., Katagiri, T., Tsunoda, T., Nakamura, Y., and Furukawa, Y. (2004). Genes associated with liver metastasis of colon cancer, identified by genome-wide cDNA microarray. Int J Oncol 24, 305–312.

    PubMed  Google Scholar 

  • Li, R., Yerganian, G., Duesberg, P., Kraemer, A., Willer, A., Rausch, C., and Hehlmann, R. (1997). Aneuploidy correlated 100% with chemical transformation of Chinese hamster cells. Proc Natl Acad Sci USA 94, 14506–14511.

    PubMed  CAS  Google Scholar 

  • Li, Y., and Benezra, R. (1996). Identification of a human mitotic checkpoint gene: hsMAD2. Science 274, 246–248.

    PubMed  CAS  Google Scholar 

  • Liao, W.T., Song, L.B., Zhang, H.Z., Zhang, X., Zhang, L., Liu, W.L., Feng, Y., Guo, B.H., Mai, H.Q., Cao, S.M., Li, M.Z., Qin, H.D., Zeng, Y.X., and Zeng, M.S. (2007). Centromere protein H is a novel prognostic marker for nasopharyngeal carcinoma progression and overall patient survival. Clin Cancer Res 13, 508–514.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Liu, S.C., Sauter, E.R., Clapper, M.L., Feldman, R.S., Levin, L., Chen, S.Y., Yen, T.J., Ross, E., Engstrom, P.F., and Klein-Szanto, A.J. (1998). Markers of cell proliferation in normal epithelia and dysplastic leukoplakias of the oral cavity. Cancer Epidemiol Biomarkers Prev 7, 597–603.

    PubMed  CAS  Google Scholar 

  • Mackay, A.M., Ainsztein, A.M., Eckley, D.M., and Earnshaw, W.C. (1998). A dominant mutant of inner centromere protein (INCENP), a chromosomal protein, disrupts prometaphase congression and cytokinesis. J Cell Biol 140, 991–1002.

    PubMed  CAS  Google Scholar 

  • Martin-Lluesma, S., Stucke, V.M., and Nigg, E.A. (2002). Role of Hec1 in spindle checkpoint signaling and kinetochore recruitment of Mad1/Mad2. Science 297, 2267–2270.

    PubMed  CAS  Google Scholar 

  • Matsuura, S., Matsumoto, Y., Morishima, K., Izumi, H., Matsumoto, H., Ito, E., Tsutsui, K., Kobayashi, J., Tauchi, H., Kajiwara, Y., Hama, S., Kurisu, K., Tahara, H., Oshimura, M., Komatsu, K., Ikeuchi, T., and Kajii, T. (2006). Monoallelic BUB1B mutations and defective mitotic-spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome. Am J Med Genet A 140, 358–367.

    PubMed  Google Scholar 

  • Michel, L., Diaz-Rodriguez, E., Narayan, G., Hernando, E., Murty, V.V., and 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, 4459–4464.

    PubMed  CAS  Google Scholar 

  • Michel, L.S., Liberal, V., Chatterjee, A., Kirchwegger, R., Pasche, B., Gerald, W., Dobles, M., Sorger, P.K., Murty, V.V., and Benezra, R. (2001). MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells. Nature 409, 355–359.

    PubMed  CAS  Google Scholar 

  • Miyoshi, Y., Iwao, K., Egawa, C., and Noguchi, S. (2001). Association of centrosomal kinase STK15/BTAK mRNA expression with chromosomal instability in human breast cancers. Int J Cancer 92, 370–373.

    PubMed  CAS  Google Scholar 

  • Moreno-Bueno, G., Sanchez-Estevez, C., Cassia, R., Rodriguez-Perales, S., Diaz-Uriarte, R., Dominguez, O., Hardisson, D., Andujar, M., Prat, J., Matias-Guiu, X., Cigudosa, J.C., and Palacios, J. (2003). Differential gene expression profile in endometrioid and nonendometrioid endometrial carcinoma: STK15 is frequently overexpressed and amplified in nonendometrioid carcinomas. Cancer Res 63, 5697–5702.

    PubMed  CAS  Google Scholar 

  • Murata-Hori, M., and Wang, Y.L. (2002). The kinase activity of aurora B is required for kinetochore-microtubule interactions during mitosis. Curr Biol 12, 894–899.

    PubMed  CAS  Google Scholar 

  • Musio, A., Montagna, C., Zambroni, D., Indino, E., Barbieri, O., Citti, L., Villa, A., Ried, T., and Vezzoni, P. (2003). Inhibition of BUB1 results in genomic instability and anchorage-independent growth of normal human fibroblasts. Cancer Res 63, 2855–2863.

    PubMed  CAS  Google Scholar 

  • Nguyen, H.G., Chinnappan, D., Urano, T., and Ravid, K. (2005). Mechanism of Aurora-B degradation and its dependency on intact KEN and A-boxes: identification of an aneuploidy-promoting property. Mol Cell Biol 25, 4977–4992.

    PubMed  CAS  Google Scholar 

  • Nishigaki, R., Osaki, M., Hiratsuka, M., Toda, T., Murakami, K., Jeang, K.T., Ito, H., Inoue, T., and Oshimura, M. (2005). Proteomic identification of differentially-expressed genes in human gastric carcinomas. Proteomics 5, 3205–3213.

    PubMed  CAS  Google Scholar 

  • Nomoto, S., Haruki, N., Takahashi, T., Masuda, A., Koshikawa, T., Takahashi, T., Fujii, Y., Osada, H., and Takahashi, T. (1999). Search for in vivo somatic mutations in the mitotic checkpoint gene, hMAD1, in human lung cancers. Oncogene 18, 7180–7183.

    PubMed  CAS  Google Scholar 

  • Nowak, M.A., Komarova, N.L., Sengupta, A., Jallepalli, P.V., Shih Ie, M., Vogelstein, B., and Lengauer, C. (2002). The role of chromosomal instability in tumor initiation. Proc Natl Acad Sci U S A 99, 16226–16231.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Ota, T., Suto, S., Katayama, H., Han, Z.B., Suzuki, F., Maeda, M., Tanino, M., Terada, Y., and Tatsuka, M. (2002). Increased mitotic phosphorylation of histone H3 attributable to AIM-1/Aurora-B overexpression contributes to chromosome number instability. Cancer Res 62, 5168–5177.

    PubMed  CAS  Google Scholar 

  • Ouellet, V., Guyot, M.C., Le Page, C., Filali-Mouhim, A., Lussier, C., Tonin, P.N., Provencher, D.M., and Mes-Masson, A.M. (2006). Tissue array analysis of expression microarray candidates identifies markers associated with tumor grade and outcome in serous epithelial ovarian cancer. Int J Cancer 119, 599–607.

    PubMed  CAS  Google Scholar 

  • Paweletz, N., Vig, B.K., and Finze, E.M. (1989). Evolution of compound centromeres. A new phenomenon. Cancer Genet Cytogenet 42, 75–86.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Perez de Castro, I., de Carcer, G., and Malumbres, M. (2007). A census of mitotic cancer genes: new insights into tumor cell biology and cancer therapy. Carcinogenesis 28, 899–912.

    Google Scholar 

  • Pils, D., Horak, P., Gleiss, A., Sax, C., Fabjani, G., Moebus, V.J., Zielinski, C., Reinthaller, A., Zeillinger, R., and Krainer, M. (2005). Five genes from chromosomal band 8p22 are significantly down-regulated in ovarian carcinoma: N33 and EFA6R have a potential impact on overall survival. Cancer 104, 2417–2429.

    PubMed  CAS  Google Scholar 

  • Pimkhaokham, A., Shimada, Y., Fukuda, Y., Kurihara, N., Imoto, I., Yang, Z.Q., Imamura, M., Nakamura, Y., Amagasa, T., and Inazawa, J. (2000). Nonrandom chromosomal imbalances in esophageal squamous cell carcinoma cell lines: possible involvement of the ATF3 and CENPF genes in the 1q32 amplicon. Jpn J Cancer Res 91, 1126–1133.

    PubMed  CAS  Google Scholar 

  • Polakis, P. (2000). Wnt signaling and cancer. Genes Dev 14, 1837–1851.

    PubMed  CAS  Google Scholar 

  • Porkka, K.P., Tammela, T.L., Vessella, R.L., and Visakorpi, T. (2004). RAD21 and KIAA0196 at 8q24 are amplified and overexpressed in prostate cancer. Genes Chromosomes Cancer 39, 1–10.

    PubMed  CAS  Google Scholar 

  • Puri, R., Tousson, A., Chen, L., and Kakar, S.S. (2001). Molecular cloning of pituitary tumor transforming gene 1 from ovarian tumors and its expression in tumors. Cancer Lett 163, 131–139.

    PubMed  CAS  Google Scholar 

  • Putkey, F.R., Cramer, T., Morphew, M.K., Silk, A.D., Johnson, R.S., McIntosh, J.R., and Cleveland, D.W. (2002). Unstable kinetochore-microtubule capture and chromosomal instability following deletion of CENP-E. Dev Cell 3, 351–365.

    PubMed  CAS  Google Scholar 

  • Rae, F.K., Hooper, J.D., Nicol, D.L., and Clements, J.A. (2001). Characterization of a novel gene, STAG1/PMEPA1, upregulated in renal cell carcinoma and other solid tumors. Mol Carcinog 32, 44–53.

    PubMed  CAS  Google Scholar 

  • Rajagopalan, H., Jallepalli, P.V., Rago, C., Velculescu, V.E., Kinzler, K.W., Vogelstein, B., and Lengauer, C. (2004). Inactivation of hCDC4 can cause chromosomal instability. Nature 428, 77–81.

    PubMed  CAS  Google Scholar 

  • Rajagopalan, H., and Lengauer, C. (2004). Aneuploidy and cancer. Nature 432, 338–341.

    PubMed  CAS  Google Scholar 

  • Rajagopalan, H., Nowak, M.A., Vogelstein, B., and Lengauer, C. (2003). The significance of unstable chromosomes in colorectal cancer. Nat Rev Cancer 3, 695–701.

    PubMed  CAS  Google Scholar 

  • Ramaswamy, S., Ross, K.N., Lander, E.S., and Golub, T.R. (2003). A molecular signature of metastasis in primary solid tumors. Nat Genet 33, 49–54.

    PubMed  CAS  Google Scholar 

  • Ru, H.Y., Chen, R.L., Lu, W.C., and Chen, J.H. (2002). hBUB1 defects in leukemia and lymphoma cells. Oncogene 21, 4673–4679.

    PubMed  CAS  Google Scholar 

  • Sakakura, C., Hagiwara, A., Yasuoka, R., Fujita, Y., Nakanishi, M., Masuda, K., Shimomura, K., Nakamura, Y., Inazawa, J., Abe, T., and Yamagishi, H. (2001). Tumour-amplified kinase BTAK is amplified and overexpressed in gastric cancers with possible involvement in aneuploid formation. Br J Cancer 84, 824–831.

    PubMed  CAS  Google Scholar 

  • Sawyers, C.L. (2001). Research on resistance to cancer drug Gleevec. Science 294, 1834.

    PubMed  CAS  Google Scholar 

  • Schumacher, J.M., Golden, A., and Donovan, P.J. (1998). AIR-2: An Aurora/Ipl1-related protein kinase associated with chromosomes and midbody microtubules is required for polar body extrusion and cytokinesis in Caenorhabditis elegans embryos. J Cell Biol 143, 1635–1646.

    PubMed  CAS  Google Scholar 

  • Sen, S., Zhou, H., Zhang, R.D., Yoon, D.S., Vakar-Lopez, F., Ito, S., Jiang, F., Johnston, D., Grossman, H.B., Ruifrok, A.C., Katz, R.L., Brinkley, W., and Czerniak, B. (2002). Amplification/overexpression of a mitotic kinase gene in human bladder cancer. J Natl Cancer Inst 94, 1320–1329.

    PubMed  CAS  Google Scholar 

  • Shackney, S.E., Smith, C.A., Miller, B.W., Burholt, D.R., Murtha, K., Giles, H.R., Ketterer, D.M., and Pollice, A.A. (1989). Model for the genetic evolution of human solid tumors. Cancer Res 49, 3344–3354.

    PubMed  CAS  Google Scholar 

  • Shaughnessy, J. (2005). Amplification and overexpression of CKS1B at chromosome band 1q21 is associated with reduced levels of p27Kip1 and an aggressive clinical course in multiple myeloma. Hematology 10 Suppl 1, 117–126.

    PubMed  CAS  Google Scholar 

  • Shi, Q., and King, R.W. (2005). Chromosome nondisjunction yields tetraploid rather than aneuploid cells in human cell lines. Nature 437, 1038–1042.

    PubMed  CAS  Google Scholar 

  • Shibata, Y., Haruki, N., Kuwabara, Y., Nishiwaki, T., Kato, J., Shinoda, N., Sato, A., Kimura, M., Koyama, H., Toyama, T., Ishiguro, H., Kudo, J., Terashita, Y., Konishi, S., and Fujii, Y. (2002). Expression of PTTG (pituitary tumor transforming gene) in esophageal cancer. Jpn J Clin Oncol 32, 233–237.

    PubMed  Google Scholar 

  • Shichiri, M., Yoshinaga, K., Hisatomi, H., Sugihara, K., and Hirata, Y. (2002). Genetic and epigenetic inactivation of mitotic checkpoint genes hBUB1 and hBUBR1 and their relationship to survival. Cancer Res 62, 13–17.

    PubMed  CAS  Google Scholar 

  • Shigeishi, H., Higashikawa, K., Ono, S., Mizuta, K., Ninomiya, Y., Yoneda, S., Taki, M., and Kamata, N. (2006). Increased expression of CENP-H gene in human oral squamous cell carcinomas harboring high-proliferative activity. Oncol Rep 16, 1071–1075.

    PubMed  CAS  Google Scholar 

  • Shigeishi, H., Mizuta, K., Higashikawa, K., Yoneda, S., Ono, S., and Kamata, N. (2005). Correlation of CENP-F gene expression with tumor-proliferating activity in human salivary gland tumors. Oral Oncol 41, 716–722.

    PubMed  CAS  Google Scholar 

  • Shih, I.M., Zhou, W., Goodman, S.N., Lengauer, C., Kinzler, K.W., and Vogelstein, B. (2001). Evidence that genetic instability occurs at an early stage of colorectal tumorigenesis. Cancer Res 61, 818–822.

    PubMed  CAS  Google Scholar 

  • Singhal, S., Amin, K.M., Kruklitis, R., DeLong, P., Friscia, M.E., Litzky, L.A., Putt, M.E., Kaiser, L.R., and Albelda, S.M. (2003). Alterations in cell cycle genes in early stage lung adenocarcinoma identified by expression profiling. Cancer Biol Ther 2, 291–298.

    PubMed  CAS  Google Scholar 

  • Sinicrope, F.A., Rego, R.L., Halling, K.C., Foster, N., Sargent, D.J., La Plant, B., French, A.J., Laurie, J.A., Goldberg, R.M., Thibodeau, S.N., and Witzig, T.E. (2006). Prognostic impact of microsatellite instability and DNA ploidy in human colon carcinoma patients. Gastroenterology 131, 729–737.

    PubMed  CAS  Google Scholar 

  • Sjoblom, T., Jones, S., Wood, L.D., Parsons, D.W., Lin, J., Barber, T.D., Mandelker, D., Leary, R.J., Ptak, J., Silliman, N., Szabo, S., Buckhaults, P., Farrell, C., Meeh, P., Markowitz, S.D., Willis, J., Dawson, D., Willson, J.K., Gazdar, A.F., Hartigan, J., Wu, L., Liu, C., Parmigiani, G., Park, B.H., Bachman, K.E., Papadopoulos, N., Vogelstein, B., Kinzler, K.W., and Velculescu, V.E. (2006). The consensus coding sequences of human breast and colorectal cancers. Science 314, 268–274.

    PubMed  Google Scholar 

  • Smith, S.L., Bowers, N.L., Betticher, D.C., Gautschi, O., Ratschiller, D., Hoban, P.R., Booton, R., Santibanez-Koref, M.F., and Heighway, J. (2005). Overexpression of aurora B kinase (AURKB) in primary non-small cell lung carcinoma is frequent, generally driven from one allele, and correlates with the level of genetic instability. Br J Cancer 93, 719–729.

    PubMed  CAS  Google Scholar 

  • Soria, J.C., Jang, S.J., Khuri, F.R., Hassan, K., Liu, D., Hong, W.K., and Mao, L. (2000). Overexpression of cyclin B1 in early-stage non-small cell lung cancer and its clinical implication. Cancer Res 60, 4000–4004.

    PubMed  CAS  Google Scholar 

  • Sotillo, R., Hernando, E., Diaz-Rodriguez, E., Teruya-Feldstein, J., Cordon-Cardo, C., Lowe, S.W., and Benezra, R. (2007). Mad2 overexpression promotes aneuploidy and tumorigenesis in mice. Cancer Cell 11, 9–23.

    PubMed  CAS  Google Scholar 

  • Stanbrough, M., Bubley, G.J., Ross, K., Golub, T.R., Rubin, M.A., Penning, T.M., Febbo, P.G., and Balk, S.P. (2006). Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res 66, 2815–2825.

    PubMed  CAS  Google Scholar 

  • Storchova, Z., and Pellman, D. (2004). From polyploidy to aneuploidy, genome instability and cancer. Nat Rev Mol Cell Biol 5, 45–54.

    PubMed  CAS  Google Scholar 

  • Strebhardt, K., and Ullrich, A. (2006). Targeting polo-like kinase 1 for cancer therapy. Nat Rev Cancer 6, 321–330.

    PubMed  CAS  Google Scholar 

  • Stroebe, H. (1893). Veber Vorkommen und Bedeutung der asymmetrischen Karyokinese, nebst Bemerkungen uber die ‘Schlummerzellen’ in der verletzten Cornea. Beitr Pathol Anat Allg Pathol 14, 154–173.

    PubMed  CAS  Google Scholar 

  • Su, M.C., Hsu, H.C., Liu, Y.J., and Jeng, Y.M. (2006). Overexpression of pituitary tumor-transforming gene-1 in hepatocellular carcinoma. Hepatogastroenterology 53, 262–265.

    PubMed  CAS  Google Scholar 

  • Suizu, F., Ryo, A., Wulf, G., Lim, J., and Lu, K.P. (2006). Pin1 regulates centrosome duplication, and its overexpression induces centrosome amplification, chromosome instability, and oncogenesis. Mol Cell Biol 26, 1463–1479.

    PubMed  CAS  Google Scholar 

  • Takahashi, Y., Miyoshi, Y., Takahata, C., Irahara, N., Taguchi, T., Tamaki, Y., and Noguchi, S. (2005). Down-regulation of LATS1 and LATS2 mRNA expression by promoter hypermethylation and its association with biologically aggressive phenotype in human breast cancers. Clin Cancer Res 11, 1380–1385.

    PubMed  CAS  Google Scholar 

  • Takeno, S., Noguchi, T., Kikuchi, R., Uchida, Y., Yokoyama, S., and Muller, W. (2002). Prognostic value of cyclin B1 in patients with esophageal squamous cell carcinoma. Cancer 94, 2874–2881.

    PubMed  CAS  Google Scholar 

  • Tanaka, T.U., Rachidi, N., Janke, C., Pereira, G., Galova, M., Schiebel, E., Stark, M.J., and Nasmyth, K. (2002). Evidence that the Ipl1-Sli15 (Aurora kinase-INCENP) complex promotes chromosome bi-orientation by altering kinetochore-spindle pole connections. Cell 108, 317–329.

    PubMed  CAS  Google Scholar 

  • Tatsuka, M., Katayama, H., Ota, T., Tanaka, T., Odashima, S., Suzuki, F., and Terada, Y. (1998). Multinuclearity and increased ploidy caused by overexpression of the aurora- and Ipl1-like midbody-associated protein mitotic kinase in human cancer cells. Cancer Res 58, 4811–4816.

    PubMed  CAS  Google Scholar 

  • Terada, Y., Tatsuka, M., Suzuki, F., Yasuda, Y., Fujita, S., and Otsu, M. (1998). AIM-1: a mammalian midbody-associated protein required for cytokinesis. Embo J 17, 667–676.

    PubMed  CAS  Google Scholar 

  • Tomonaga, T., Matsushita, K., Ishibashi, M., Nezu, M., Shimada, H., Ochiai, T., Yoda, K., and Nomura, F. (2005). Centromere protein H is up-regulated in primary human colorectal cancer and its overexpression induces aneuploidy. Cancer Res 65, 4683–4689.

    PubMed  CAS  Google Scholar 

  • Tomonaga, T., Matsushita, K., Yamaguchi, S., Oohashi, T., Shimada, H., Ochiai, T., Yoda, K., and Nomura, F. (2003). Overexpression and mistargeting of centromere protein-A in human primary colorectal cancer. Cancer Res 63, 3511–3516.

    PubMed  CAS  Google Scholar 

  • Torres, E.M., Sokolsky, T., Tucker, C.M., Chan, L.Y., Boselli, M., Dunham, M.J., and Amon, A. (2007). Effects of aneuploidy on cellular physiology and cell division in haploid yeast. Science 317, 916–924.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Van Hooser, A.A., Ouspenski, II, Gregson, H.C., Starr, D.A., Yen, T.J., Goldberg, M.L., Yokomori, K., Earnshaw, W.C., Sullivan, K.F., and Brinkley, B.R. (2001). Specification of kinetochore-forming chromatin by the histone H3 variant CENP-A. J Cell Sci 114, 3529–3542.

    Google Scholar 

  • Wang, T.L., Diaz, L.A., Jr., Romans, K., Bardelli, A., Saha, S., Galizia, G., Choti, M., Donehower, R., Parmigiani, G., Shih Ie, M., Iacobuzio-Donahue, C., Kinzler, K.W., Vogelstein, B., Lengauer, C., and Velculescu, V.E. (2004a). Digital karyotyping identifies thymidylate synthase amplification as a mechanism of resistance to 5-fluorouracil in metastatic colorectal cancer patients. Proc Natl Acad Sci USA 101, 3089–3094.

    Google Scholar 

  • Wang, X., Jin, D.Y., Ng, R.W., Feng, H., Wong, Y.C., Cheung, A.L., and Tsao, S.W. (2002). Significance of MAD2 expression to mitotic checkpoint control in ovarian cancer cells. Cancer Res 62, 1662–1668.

    PubMed  CAS  Google Scholar 

  • Wang, X., Jin, D.Y., Wong, Y.C., Cheung, A.L., Chun, A.C., Lo, A.K., Liu, Y., and Tsao, S.W. (2000). Correlation of defective mitotic checkpoint with aberrantly reduced expression of MAD2 protein in nasopharyngeal carcinoma cells. Carcinogenesis 21, 2293–2297.

    PubMed  CAS  Google Scholar 

  • Wang, X., Zhou, Y.X., Qiao, W., Tominaga, Y., Ouchi, M., Ouchi, T., and Deng, C.X. (2006). Overexpression of aurora kinase A in mouse mammary epithelium induces genetic instability preceding mammary tumor formation. Oncogene 25, 7148–7158.

    PubMed  CAS  Google Scholar 

  • Wang, Y., Zhou, X., Zhu, H., Liu, S., Zhou, C., Zhang, G., Xue, L., Lu, N., Quan, L., Bai, J., Zhan, Q., and Xu, N. (2005). Overexpression of EB1 in human esophageal squamous cell carcinoma (ESCC) may promote cellular growth by activating beta-catenin/TCF pathway. Oncogene 24, 6637–6645.

    PubMed  CAS  Google Scholar 

  • Wang, Z., Cummins, J.M., Shen, D., Cahill, D.P., Jallepalli, P.V., Wang, T.L., Parsons, D.W., Traverso, G., Awad, M., Silliman, N., Ptak, J., Szabo, S., Willson, J.K., Markowitz, S.D., Goldberg, M.L., Karess, R., Kinzler, K.W., Vogelstein, B., Velculescu, V.E., and Lengauer, C. (2004b). Three classes of genes mutated in colorectal cancers with chromosomal instability. Cancer Res 64, 2998–3001.

    Google Scholar 

  • Watanabe, T., Wu, T.T., Catalano, P.J., Ueki, T., Satriano, R., Haller, D.G., Benson, A.B., 3rd, and Hamilton, S.R. (2001). Molecular predictors of survival after adjuvant chemotherapy for colon cancer. N Engl J Med 344, 1196–1206.

    PubMed  CAS  Google Scholar 

  • Weaver, B.A., Bonday, Z.Q., Putkey, F.R., Kops, G.J., Silk, A.D., and Cleveland, D.W. (2003). Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss. J Cell Biol 162, 551–563.

    PubMed  CAS  Google Scholar 

  • Weaver, B.A., and Cleveland, D.W. (2005). Decoding the links between mitosis, cancer, and chemotherapy: The mitotic checkpoint, adaptation, and cell death. Cancer Cell 8, 7–12.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Wikman, H., Kettunen, E., Seppanen, J.K., Karjalainen, A., Hollmen, J., Anttila, S., and Knuutila, S. (2002). Identification of differentially expressed genes in pulmonary adenocarcinoma by using cDNA array. Oncogene 21, 5804–5813.

    PubMed  CAS  Google Scholar 

  • Wong, Y.F., Cheung, T.H., Tsao, G.S., Lo, K.W., Yim, S.F., Wang, V.W., Heung, M.M., Chan, S.C., Chan, L.K., Ho, T.W., Wong, K.W., Li, C., Guo, Y., Chung, T.K., and Smith, D.I. (2006). Genome-wide gene expression profiling of cervical cancer in Hong Kong women by oligonucleotide microarray. Int J Cancer 118, 2461–2469.

    PubMed  CAS  Google Scholar 

  • Yuan, B., Xu, Y., Woo, J.H., Wang, Y., Bae, Y.K., Yoon, D.S., Wersto, R.P., Tully, E., Wilsbach, K., and Gabrielson, E. (2006). Increased expression of mitotic checkpoint genes in breast cancer cells with chromosomal instability. Clin Cancer Res 12, 405–410.

    PubMed  CAS  Google Scholar 

  • Yuan, J., Horlin, A., Hock, B., Stutte, H.J., Rubsamen-Waigmann, H., and Strebhardt, K. (1997). Polo-like kinase, a novel marker for cellular proliferation. Am J Pathol 150, 1165–1172.

    PubMed  CAS  Google Scholar 

  • Yuen, K.W., Montpetit, B., and Hieter, P. (2005). The kinetochore and cancer: what's the connection? Curr Opin Cell Biol 17, 576–582.

    PubMed  CAS  Google Scholar 

  • Zeitlin, S.G., Shelby, R.D., and Sullivan, K.F. (2001). CENP-A is phosphorylated by Aurora B kinase and plays an unexpected role in completion of cytokinesis. J Cell Biol 155, 1147–1157.

    PubMed  CAS  Google Scholar 

  • Zetterberg, A., and Esposti, P.L. (1980). Prognostic significance of nuclear DNA levels in prostatic carcinoma. Scand J Urol Nephrol Suppl 55, 53–58.

    PubMed  CAS  Google Scholar 

  • Zhang, D., Hirota, T., Marumoto, T., Shimizu, M., Kunitoku, N., Sasayama, T., Arima, Y., Feng, L., Suzuki, M., Takeya, M., and Saya, H. (2004). Cre-loxP-controlled periodic Aurora-A overexpression induces mitotic abnormalities and hyperplasia in mammary glands of mouse models. Oncogene 23, 8720–8730.

    PubMed  CAS  Google Scholar 

  • Zhou, H., Kuang, J., Zhong, L., Kuo, W.L., Gray, J.W., Sahin, A., Brinkley, B.R., and Sen, S. (1998). Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nat Genet 20, 189–193.

    PubMed  CAS  Google Scholar 

  • Zhou, W., Goodman, S.N., Galizia, G., Lieto, E., Ferraraccio, F., Pignatelli, C., Purdie, C.A., Piris, J., Morris, R., Harrison, D.J., Paty, P.B., Culliford, A., Romans, K.E., Montgomery, E.A., Choti, M.A., Kinzler, K.W., and Vogelstein, B. (2002). Counting alleles to predict recurrence of early-stage colorectal cancers. Lancet 359, 219–225.

    PubMed  Google Scholar 

  • Zhu, X., Mao, Z., Na, Y., Guo, Y., Wang, X., and Xin, D. (2006). Significance of pituitary tumor transforming gene 1 (PTTG1) in prostate cancer. Anticancer Res 26, 1253–1259.

    PubMed  CAS  Google Scholar 

  • Zou, H., McGarry, T.J., Bernal, T., and Kirschner, M.W. (1999). Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis. Science 285, 418–422.

    PubMed  CAS  Google Scholar 

  • Zumbrunn, J., Kinoshita, K., Hyman, A.A., and Nathke, I.S. (2001). Binding of the adenomatous polyposis coli protein to microtubules increases microtubule stability and is regulated by GSK3 beta phosphorylation. Curr Biol 11, 44–49.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan

    Takeshi Tomonaga

Authors
  1. Takeshi Tomonaga
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Takeshi Tomonaga .

Editor information

Editors and Affiliations

  1. Dipto. Oncologia Sperimentale, Istituto Europeo di Oncologia, Via Adamello 16, Milano, 20139, Italy

    Peter De Wulf

  2. Animal & Population Biology, Inst. Cell & Molecular Biology, University of Edinburgh, West Mains Road, Edinburgh, EH9 3JT, United Kingdom

    William C. Earnshaw

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Tomonaga, T. (2009). The Kinetochore-Cancer Connection. In: De Wulf, P., Earnshaw, W. (eds) The Kinetochore:. Springer, New York, NY. https://doi.org/10.1007/978-0-387-69076-6_14

Download citation

Publish with us

Policies and ethics

Search

Navigation