Submitted: 28 March 2007 Accepted: 28 August 2007 References Alsop, G.B., and D. Zhang. 2003. Microtubules are the only structural constitu- ent of the spindle apparatus required for induction of cell cleavage. J. Cell Biol. 162:383–390. Cardoso, J., L. Molenaar, R.X. de Menezes, M. van Leerdam, C. Rosenberg, G. Moslein, J. Sampson, H. Morreau, J.M. Boer, and R. Fodde. 2006. Chromosomal instability in MYH- and APC-mutant adenomatous pol- yps. Cancer Res. 66:2514–2519. D’Avino, P.P., M.S. Savoian, and D.M. Glover. 2005. Cleavage furrow formation and ingression during animal cytokinesis: a microtubule legacy. J. Cell Sci. 118:1549–1558. Draviam, V.M., I. Shapiro, B. Aldridge, and P.K. Sorger. 2006. Misorientation and reduced stretching of aligned sister kinetochores promote chromosome missegregation in EB1- or APC-depleted cells. EMBO J. 25:2814–2827. Duesberg, P., and R. Li. 2003. Multistep carcinogenesis: a chain reaction of aneuploidizations. Cell Cycle. 2:202–210. Fearnhead, N.S., M.P. Britton, and W.F. Bodmer. 2001. The ABC of APC. Hum. Mol. Genet. 10:721–733. Fodde, R., J. Kuipers, C. Rosenberg, R. Smits, M. Kielman, C. Gaspar, J.H. van Es, C. Breukel, J. Wiegant, R.H. Giles, and H. Clevers. 2001. Mutations in the APC tumour suppressor gene cause chromosomal instability. Nat. Cell Biol. 3:433–438. Fujiwara, T., M. Bandi, M. Nitta, E.V. Ivanova, R.T. Bronson, and D. Pellman. 2005. Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells. Nature. 437:1043–1047. Ganem, N.J., Z. Storchova, and D. Pellman. 2007. Tetraploidy, aneuploidy and cancer. Curr. Opin. Genet. Dev. 17:157–162. Glotzer, M. 2001. Animal cell cytokinesis. Annu. Rev. Cell Dev. Biol. 17:351–386. Green, R.A., and K.B. Kaplan. 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. Green, R.A., R. Wollman, and K.B. Kaplan. 2005. APC and EB1 function to- gether in mitosis to regulate spindle dynamics and chromosome alignment. Mol. Biol. Cell. 16:4609–4622. Haigis, K.M., J.G. Caya, M. Reichelderfer, and W.F. Dove. 2002. Intestinal adenomas can develop with a stable karyotype and stable microsatellites. Proc. Natl. Acad. Sci. USA. 99:8927–8931. Inoue, Y.H., M.S. Savoian, T. Suzuki, E. Mathe, M.T. Yamamoto, and D.M. Glover. 2004. Mutations in orbit/mast reveal that the central spindle is comprised of two microtubule populations, those that initiate cleavage and those that propagate furrow ingression. J. Cell Biol. 166:49–60. Lamlum, H., M. Ilyas, A. Rowan, S. Clark, V. Johnson, J. Bell, I. Frayling, J. Efstathiou, K. Pack, S. Payne, et al. 1999. The type of somatic mutation at APC in familial adenomatous polyposis is determined by the site of the germline mutation: a new facet to Knudson’s ‘two-hit’ hypothesis. Nat. Med. 5:1071–1075. Lengauer, C., K.W. Kinzler, and B. Vogelstein. 1997. Genetic instability in colorectal cancers. Nature. 386:623–627. Marshman, E., C. Booth, and C.S. Potten. 2002. The intestinal epithelial stem cell. Bioessays. 24:91–98. Merlo, L.M., J.W. Pepper, B.J. Reid, and C.C. Maley. 2006. Cancer as an evolu- tionary and ecological process. Nat. Rev. Cancer. 6:924–935. Morrison, E.E., B.N. Wardleworth, J.M. Askham, A.F. Markham, and D.M. Meredith. 1998. EB1, a protein which interacts with the APC tumour suppressor, is associated with the microtubule cytoskeleton throughout the cell cycle. Oncogene. 17:3471–3477. Moser, A.R., H.C. Pitot, and W.F. Dove. 1990. A dominant mutation that predis- poses to multiple intestinal neoplasia in the mouse. Science. 247:322–324. Munemitsu, S., B. Souza, O. Muller, I. Albert, B. Rubinfeld, and P. Polakis. 1994. The APC gene product associates with microtubules in vivo and promotes their assembly in vitro. Cancer Res. 54:3676–3681. Nowell, P.C. 1976. The clonal evolution of tumor cell populations. Science. 194:23–26. Pihan, G.A., J. Wallace, Y. Zhou, and S.J. Doxsey. 2003. Centrosome abnormali- ties and chromosome instability occur together in pre-invasive carcinomas. Cancer Res. 63:1398–1404. Rappaport, R. 1961. Experiments concerning the cleavage stimulus in sand dol- lar eggs. J. Exp. Zool. 148:81–89. Reinsch, S., and E. Karsenti. 1994. Orientation of spindle axis and distribution of plasma membrane proteins during cell division in polarized MDCKII cells. J. Cell Biol. 126:1509–1526. 1120 JCB • VOLUME 178 • NUMBER 7 • 2007 Saint, R., and W.G. Somers. 2003. Animal cell division: a fellowship of the dou- ble ring? J. Cell Sci. 116:4277–4281. Shi, Q., and R.W. King. 2005. Chromosome nondisjunction yields tetraploid rather than aneuploid cells in human cell lines. Nature. 437:1038–1042. Shih, I.M., W. Zhou, S.N. Goodman, C. Lengauer, K.W. Kinzler, and B. Vogelstein. 2001. Evidence that genetic instability occurs at an early stage of colorectal tumorigenesis. Cancer Res. 61:818–822. Sieber, O.M., I.P. Tomlinson, and H. Lamlum. 2000. The adenomatous polyposis coli (APC) tumour suppressor–genetics, function and disease. Mol. Med. Today. 6:462–469. Smith, K.J., D.B. Levy, P. Maupin, T.D. Pollard, B. Vogelstein, and K.W. Kinzler. 1994. Wild-type but not mutant APC associates with the microtubule cytoskeleton. Cancer Res. 54:3672–3675. Storchova, Z., and D. Pellman. 2004. From polyploidy to aneuploidy, genome instability and cancer. Nat. Rev. Mol. Cell Biol. 5:45–54. Storchova, Z., A. Breneman, J. Cande, J. Dunn, K. Burbank, E. O’Toole, and D. Pellman. 2006. Genome-wide genetic analysis of polyploidy in yeast. Nature. 443:541–547. Su, L.K., M. Burrell, D.E. Hill, J. Gyuris, R. Brent, R. Wiltshire, J. Trent, B. Vogelstein, and K.W. Kinzler. 1995. APC binds to the novel protein EB1. Cancer Res. 55:2972–2977. Thatcher, K.N., S. Peddada, D.H. Yasui, and J.M. Lasalle. 2005. Homologous pairing of 15q11-13 imprinted domains in brain is developmentally regulated but deficient in Rett and autism samples. Hum. Mol. Genet. 14:785–797. Tighe, A., V.L. Johnson, and S.S. Taylor. 2004. Truncating APC mutations have dominant effects on proliferation, spindle checkpoint control, survival and chromosome stability. J. Cell Sci. 117:6339–6353. Wang, Q., Y. Hirohashi, K. Furuuchi, H. Zhao, Q. Liu, H. Zhang, R. Murali, A. Berezov, X. Du, B. Li, and M.I. Greene. 2004. The centrosome in normal and transformed cells. DNA Cell Biol. 23:475–489. Wheatley, S.P., and Y. Wang. 1996. Midzone microtubule bundles are continu- ously required for cytokinesis in cultured epithelial cells. J. Cell Biol. 135:981–989.