The Role of APC in Mitosis and in Chromosome Instability

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 656)

Abstract

The established role of APC in regulating microtubules and actin in polarized epithelia naturally raises the possibility that APC similarly influences the mitotic cytoskeleton. The recent accumulation of experimental evidence in mitotic cells supports this supposition. APC associates with mitotic spindle microtubules, most notably at the plus-ends of microtubules that interact with kinetochores. Genetic experiments implicate APC in the regulation of spindle microtubule dynamics, probably through its interaction with the microtubule plus-end binding protein, EB1. Moreover, functional data show that APC modulates kinetochore-microtubule attachments and is required for the spindle checkpoint to detect transiently misaligned chromosomes. Together this evidence points to a role for APC in maintaining mitotic fidelity. Such a role is particularly significant when considered in the context of the chromosome instability observed in colorectal tumors bearing mutations in APC. The prevalence of APC truncation mutants in colorectal tumors and the ability ofthese alleles to act dominantly to inhibit the mitotic spindle place chromosome instability at the earliest stage of colorectal cancer progression (Le., prior to deregulation of β-catenin). This may contribute to the autosomal dominant predisposition of patients with familial adenomatous polyposis to develop colon cancer. In this chapter, we will review the literature linking APC to regulation of mitotic fidelity and discuss the implications for dividing epithelial cells in the intestine.

Keywords

Migration Codon Adenoma Oligomerization Assure 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Siegrist SE, Doe CQ. Microtubule-induced cortical cell polarity. Genes Dev 2007; 21(5):483–496.CrossRefPubMedGoogle Scholar
  2. 2.
    Basu R, Chang F. Shaping the actin cytoskeleton using microtubule tips. Curr Opin Cell Biol 2007; 19(1):88–94.CrossRefPubMedGoogle Scholar
  3. 3.
    Etienne-Manneville S, Hall A. Cdc42 regulates GSK-3beta and adenomatous polyposis coli to control cell polarity. Nature 13 2003; 421(6924):753–756.CrossRefGoogle Scholar
  4. 4.
    Nathke IS, Adams CL, Polakis P et al. The adenomatous polyposis coli tumor suppressor protein localizes to plasma membrane sites involved in active cell migration. J Cell Biol 1996; 134(1):165–179.CrossRefPubMedGoogle Scholar
  5. 5.
    Mimori-Kiyosue Y, Shiina N, Tsukita S. The dynamic behavior of the APC-binding protein EB1 on the distal ends of microtubules. Curr Biol 2000; 10(14):865–868.CrossRefPubMedGoogle Scholar
  6. 6.
    Yamana N, Arakawa Y, Nishino T et al. The Rho-mDial pathway regulates cell polarity and focal adhesion turnover in migrating cells through mobilizing Ape and c-Src. Mol Cell Biol 2006; 26(18):6844–6858.CrossRefPubMedGoogle Scholar
  7. 7.
    Wen Y, Eng CH, Schmoranzer J et al. EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration. Nat Cell Biol 2004; 6(9):820–830.CrossRefPubMedGoogle Scholar
  8. 8.
    Gundersen GG, Gomes ER, Wen Y. Cortical control of microtubule stability and polarization. Curr Opin Cell Biol 2004; 16(1):106–112.CrossRefPubMedGoogle Scholar
  9. 9.
    Cleveland DW, Mao Y, Sullivan KF. Centromeres and kinetochores: from epigenetics to mitotic checkpoint signaling. Cell 2003; 112(4):407–421.CrossRefPubMedGoogle Scholar
  10. 10.
    Kline-Smith SL, Sandall S, Desai A. Kinetochore-spindle microtubule interactions during mitosis. Curr Opin Cell Biol 2005; 17(1):35–46.CrossRefPubMedGoogle Scholar
  11. 11.
    Fodde R, Kuipers J, Rosenberg C et al. Mutations in the APC tumour suppressor gene cause chromosomal instability. Nat Cell Biol 2001; 3(4):433–438.CrossRefPubMedGoogle Scholar
  12. 12.
    Kaplan KB, Burds AA, Swedlow JR et al. A role for the Adenomatous Polyposis Coli protein in chromosome segregation. Nat Cell Biol 2001; 3(4):429–432.CrossRefPubMedGoogle Scholar
  13. 13.
    Green RA, Kaplan KB. 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 2003; 163(5):949–961.CrossRefPubMedGoogle Scholar
  14. 14.
    Zumbrunn J, Kinoshita K, Hyman AA et al. Binding of the adenomatous polyposis coli protein to microtubules increases microtubule stability and is regulated by GSK3 beta phosphorylation. Curr Biol 2001; 11(1):44–49.CrossRefPubMedGoogle Scholar
  15. 15.
    Lengauer C, Kinzler KW, Vogelstein B. Genetic instability in colorectal cancers. Nature 1997; 386(6625):623–627.CrossRefPubMedGoogle Scholar
  16. 16.
    Tighe A, Johnson VL, Taylor SS. Truncating APC mutations have dominant effects on proliferation, spindle checkpoint control, survival and chromosome stability. J Cell Sci 2004; 117(Pt 26):6339–6353.CrossRefPubMedGoogle Scholar
  17. 17.
    Green RA, Wollman R, Kaplan KB. APC and EB1 Function Together in Mitosis to Regulate Spindle Dynamics and Chromosome Alignment. Mol Biol Cell 2005; 16(10):4609–4622.CrossRefPubMedGoogle Scholar
  18. 18.
    Carvalho P, Tirnauer JS, Pellman D. Surfing on microtubule ends. Trends Cell Biol 2003; 13(5):229–237.CrossRefPubMedGoogle Scholar
  19. 19.
    Piehl M, Tulu US, Wadsworth P et al. Centrosome maturation: measurement of microtubule nucleation throughout the cell cycle by using GFP-tagged EB1. Proc Natl Acad Sci USA 2004; 101(6):1584–1588.CrossRefPubMedGoogle Scholar
  20. 20.
    Holy TE, Leibler S. Dynamic instability of microtubules as an efficient way to search in space. Proc Natl Acad Sci USA 1994; 91(12):5682–5685.CrossRefPubMedGoogle Scholar
  21. 21.
    Schuyler SC, Pellman D. Search, capture and signal: games microtubules and centrosomes play. J Cell Sci 2001; 114(Pt 2):247–255.PubMedGoogle Scholar
  22. 22.
    Wollman R, Cytrynbaum EN, Jones JT et al. Efficient chromosome capture requires a bias in the’ search-and-capture’ process during mitotic-spindle assembly. Curr Biol 2005; 15(9):828–832.CrossRefPubMedGoogle Scholar
  23. 23.
    Jimbo T, Kawasaki I, Koyama R et al. Identification of a link between the tumour suppressor APC and the kinesin superfamily. Nat Cell Biol 2002; 4(4):323–327.CrossRefPubMedGoogle Scholar
  24. 24.
    Deka J, Kuhlmann J, Muller O. A domain within the tumor suppressor protein APC shows very similar biochemical properties as the microtubule-associated protein tau. Eur J Biochem 1998; 253(3):591–597.CrossRefPubMedGoogle Scholar
  25. 25.
    Bu W, Su LK. Characterization of functional domains of human EB1 family proteins. J Biol Chem 2003; 278(50):49721–49731.CrossRefPubMedGoogle Scholar
  26. 26.
    Slep KC, Rogers SL, Elliott SL et al. Structural determinants for EB1-mediated recruitment of APC and spectraplakins to the microtubule plus end. J Cell Biol 2005; 168(4):587–598.CrossRefPubMedGoogle Scholar
  27. 27.
    Kita K, Wittmann T, Nathke IS et al. Adenomatous polyposis coli on microtubule plus ends in cell extensions can promote microtubule net growth with or without EB1. Mol Biol Cell 2006; 17(5):2331–2345.CrossRefPubMedGoogle Scholar
  28. 28.
    Barth AI, Siemers KA, Nelson WJ. Dissecting interactions between EB1, microtubules and APC in cortical clusters at the plasma membrane. J Cell Sci 2002; 115(Pt 8):1583–1590.PubMedGoogle Scholar
  29. 29.
    Sharma M, Leung L, Brocardo M et al. Membrane localization of adenomatous polyposis coli protein at cellular protrusions: targeting sequences and regulation by beta-catenin. J Biol Chem 2006; 281(25):17140–17149.CrossRefPubMedGoogle Scholar
  30. 30.
    Ciani L, Krylova O, Smalley MJ et al. A divergent canonical WNT-signaling pathway regulates microtubule dynamics: Dishevelled signals locally to stabilize microtubules. J Cell Biol 2004; 164(2):243–253.CrossRefPubMedGoogle Scholar
  31. 31.
    Votin V, Nelson WJ, Barth AI. Neurite outgrowth involves adenomatous polyposis coli protein and beta-carenin. J Cell Sci 2005; 118(Pt 24):5699–5708.CrossRefPubMedGoogle Scholar
  32. 32.
    Mahadevaiyer S, Xu C, Gumbiner BM. Characterization of a 60S complex of the adenomatous polyposis coli tumor suppressor protein. Biochim Biophys Acta 2007; 1773(2):120–130.CrossRefPubMedGoogle Scholar
  33. 33.
    Reinacher-Schick A, Gumbiner BM. Apical membrane localization of the adenomatous polyposis coli tumor suppressor protein and subcellular distribution of the beta-catenin destruction complex in polarized epithelial cells. J Cell Biol 2001; 152(3):491–502.CrossRefPubMedGoogle Scholar
  34. 34.
    Penman GA, Leung L, Nathke IS. The adenomatous polyposis coli protein (APC) exists in two distinct soluble complexes with different functions. J Cell Sci 2005; 118(Pt 20):4741–4750.CrossRefPubMedGoogle Scholar
  35. 35.
    Wu XS, Tsan GL, Hammer JA 3rd. Melanophilin and myosin Va track the microtubule plus end on EB1. J Cell Biol 2005; 171(2):201–207.CrossRefPubMedGoogle Scholar
  36. 36.
    Kawasaki Y, Senda T, Ishidate T et al. Asef, a link between the tumor suppressor APC and G-protein signaling. Science 2000; 289(5482):1194–1197.CrossRefPubMedGoogle Scholar
  37. 37.
    Rosin-Arbesfeld R, Ihrke G, Bienz M. Actin-dependent membrane association of the APC tumour suppressor in polarized mammalian epithelial cells. EMBO J 2001; 20(21):5929–5939.CrossRefPubMedGoogle Scholar
  38. 38.
    Kawasaki I, Sato R, Akiyama T. Mutated APC and Asef are involved in the migration of colorectal tumour cells. Nat Cell Biol 2003; 5(3):211–215.CrossRefPubMedGoogle Scholar
  39. 39.
    Ligon LA, Shelly SS, Tokiro M et al. The microtubule plus-end proteins EB1 and dynactin have differential effects on microtubule polymerization. Mol Biol Cell 2003; 14(4):1405–1417.CrossRefPubMedGoogle Scholar
  40. 40.
    Watanabe T, Wang S, Noritake J et al. Interaction with IQGAP1 links APC to Rae1, Cdc42 and actin filaments during cell polarization and migration. Dev Cell 2004; 7(6):871–883.CrossRefPubMedGoogle Scholar
  41. 41.
    Wassmann K, Benezra R. Mitotic checkpoints: from yeast to cancer. Curr Opin Genet Dev 2001; 11(1):83–90.CrossRefPubMedGoogle Scholar
  42. 42.
    Draviam VM, Xie S, Sorger PK. Chromosome segregation and genomic stability. Curr Opin Genet Dev 2004; 14(2):120–125.CrossRefPubMedGoogle Scholar
  43. 43.
    Jallepalli PV, Lengauer C. Chromosome segregation and cancer: cutting through the mystery. Nat Rev Cancer 2001; 1(2):109–117.CrossRefPubMedGoogle Scholar
  44. 44.
    Taylor SS, Scott MI, Holland AJ. The spindle checkpoint: a quality control mechanism which ensures accurate chromosome segregation. Chromosome Res 2004; 12(6):599–616.CrossRefPubMedGoogle Scholar
  45. 45.
    Draviam VM, Shapiro I, Aldridge B et al. Misorientation and reduced stretching of aligned sister kinetochores promote chromosome missegregation in EB1-or APC-depleted cells. EMBO J 2006; 25(12):2814–2827.CrossRefPubMedGoogle Scholar
  46. 46.
    Dikovskaya D, Schiffmann D, Newton IP et al. Loss of APC induces polyploidy as a result of a combination of defects in mitosis and apoptosis. J Cell Biol 2007; 176(2):183–195.CrossRefPubMedGoogle Scholar
  47. 47.
    Salmon ED, Cimini D, Cameron LA et al. Merotelic kinetochores in mammalian tissue cells. Philos Trans R Soc Lond B Biol Sci 2005; 360(1455):553–568.CrossRefPubMedGoogle Scholar
  48. 48.
    Shelby RD, Hahn KM, Sullivan KF. Dynamic elastic behavior of alpha-satellite DNA domains visualized in situ in living human cells. J Cell Biol 1996; 135(3):545–557.CrossRefPubMedGoogle Scholar
  49. 49.
    He X, Rines DR, Espelin CW et al. Molecular analysisof kinetochore-microtubule attachment in budding yeast. Cell 2001; 106(2):195–206.CrossRefPubMedGoogle Scholar
  50. 50.
    Rappaport R. Establishment of the mechanism of cytokinesis in animal cells. Int Rev Cytol 1986; 105:245–281.CrossRefPubMedGoogle Scholar
  51. 51.
    Caldwell CM, Green RA, Kaplan KB. APC mutations lead to cytokinetic failures in vitro and tetraploid genotypes in Min mice. J Cell Biol 2007; 178(7):1109–1120.CrossRefPubMedGoogle Scholar
  52. 52.
    Rappaport R. Cleavage furrow establishment by the moving mitotic apparatus. Dev Growth Differ 1997; 39(2):221–226.CrossRefPubMedGoogle Scholar
  53. 53.
    Bement WM, Benink HA, von Dassow G. A microtubule-dependent zone of active RhoA during cleavage plane specification. J Cell Biol 2005; 170(1):91–101.CrossRefPubMedGoogle Scholar
  54. 54.
    McCartney BM, Price MH, Webb RL et al. Testing hypotheses for the functions of APC family proteins using null and truncation alleles in Drosophila. Development 2006; 133(12):2407–2418.CrossRefPubMedGoogle Scholar
  55. 55.
    Strickland LI, Donnelly EJ, Burgess DR. Induction of cytokinesis is independent of precisely regulated microtubule dynamics. Mol Biol Cell 2005; 16(10):4485–4494.CrossRefPubMedGoogle Scholar
  56. 56.
    Shannon KB, Canman JC, Ben Moree C et al. Taxol-stabilized microtubules can position the cytokinetic furrow in mammalian cells. Mol Biol Cell 2005; 16(9):4423–4436.CrossRefPubMedGoogle Scholar
  57. 57.
    Strickland LI, Wen Y, Gundersen GG et al. Interaction between EB1 and p150g1ued is required for anaphase astral microtubule elongation and stimulation of cytokinesis. Curr Biol 2005; 15(24):2249–2255.CrossRefPubMedGoogle Scholar
  58. 58.
    McCartney BM, McEwen DG, Grevengoed E et al. Drosophila APC2 and Armadillo participate in tethering mitotic spindles to cortical actin. Nat Cell Biol 2001; 3(10):933–938.CrossRefPubMedGoogle Scholar
  59. 59.
    Chen HJ, Lin CM, Lin CS et al. The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling pathway. Genes Dev 2006; 20(14):1933–1945.CrossRefPubMedGoogle Scholar
  60. 60.
    Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med 2003; 348(10):919–932.CrossRefPubMedGoogle Scholar
  61. 61.
    Bienz M. The subcellular destinations of APC proteins. Nat Rev Mol Cell Biol 2002; 3(5):328–338.CrossRefPubMedGoogle Scholar
  62. 62.
    Faux MC, Ross JL, Meeker C et al. Restoration of full-length adenomatous polyposis coli (APC) protein in a colon cancer cell line enhances cell adhesion. J Cell Sci 2004; 117(Pt 3):427–439.PubMedGoogle Scholar
  63. 63.
    Waterman-Storer CM, Worthylake RA, Liu BP et al. Microtubule growth activates Rac1 to promote lamellipodial protrusion in fibroblasts. Nat Cell Biol 1999; 1(1):45–50.CrossRefPubMedGoogle Scholar
  64. 64.
    Kroboth K, Newton IP, Kita K, et al. Lack of adenomatous polyposis coli protein correlateswith a decrease in cell migration and overall changes in microtubule stability. Mol Biol Cell 2006; 18(3):910–918.CrossRefPubMedGoogle Scholar
  65. 65.
    Nathke IS. The adenomatous polyposis coli protein: the Achilles heel of the gut epithelium. Annu Rev Cell Dev Biol 2004; 20:337–366.CrossRefPubMedGoogle Scholar
  66. 66.
    Yamashita YM, Jones DL, Fuller MT. Orientation of asymmetric stem cell division by the APC tumor suppressor and centrosome. Science 2003; 301(5639):1547–1550.CrossRefPubMedGoogle Scholar
  67. 67.
    Roegiers F, Jan YN. Asymmetric cell division. Curr Opin Cell Biol 2004; 16(2):195–205.CrossRefPubMedGoogle Scholar
  68. 68.
    Zimonjic D, Brooks MW, Popescu N et al. Derivation of human tumor cells in vitro without widespread genomic instability. Cancer Res 2001; 61(24):8838–8844.PubMedGoogle Scholar
  69. 69.
    Duesberg P, Li R. Multistep carcinogenesis: a chain reaction of aneuploidizations. Cell Cycle 2003; 2(3):202–210.PubMedGoogle Scholar
  70. 70.
    Lin H, de Carvalho P, Kho D et al. Polyploids require Bikl for kinetochore-microtubule attachment. J Cell Biol 2001; 155(7):1173–1184.CrossRefPubMedGoogle Scholar
  71. 71.
    Storchova Z, Breneman A, Cande J et al. Genome-wide genetic analysis of polyploidy in yeast. Nature 2006; 443(7111):541–547.CrossRefPubMedGoogle Scholar
  72. 72.
    Shi Q, King RW. Chromosome nondisjunction yields tetraploid rather than aneuploid cells in human cell lines. Nature 2005; 437(7061):1038–1042.CrossRefPubMedGoogle Scholar
  73. 73.
    Fujiwara T, Bandi M, Nitta M et al. Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells. Nature 2005; 437(7061):1043–1047.CrossRefPubMedGoogle Scholar
  74. 74.
    Storchova Z, Pellman D. From polyploidy to aneuploidy, genome instability and cancer. Nat Rev Mol Cell Biol 2004; 5(1):45–54.CrossRefPubMedGoogle Scholar
  75. 75.
    Rowan AJ, Lamlum H, Ilyas M et al. APC mutations in sporadic coloreetal tumors: A mutational “hotspot” and interdependence of the “two hits”. Proc Natl Acad Sci USA 2000; 97(7):3352–3357.CrossRefPubMedGoogle Scholar
  76. 76.
    Abdel-Rahman WM, Katsura K, Rens W et al. Spectral karyotyping suggests additional subsets of colorectal cancers characterized by pattern of chromosome rearrangement. Proc Natl Acad Sci USA 2001; 98(5):2538–2543.CrossRefPubMedGoogle Scholar
  77. 77.
    Haigis KM, Caya JG, Reichelderfer M et al. Intestinal adenomas can develop with a stable karyotype and stable microsatellites. Proc Natl Acad Sci USA 2002; 99(13):8927–8931.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  1. 1.Section of Molecular and Cellular BiologyUniversity of California, DavisDavisUSA

Personalised recommendations