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Non-motor Spindle Proteins as Cancer Chemotherapy Targets

  • Robert L. MargolisEmail author
  • Mythili Yenjerla
Chapter

Abstract

The mitotic spindle consists of a highly organized fusiform array of microtubules which functions to precisely segregate chromosomes during cell division. Both motor and non-motor microtubule associated proteins (MAPs) promote the assembly and disassembly of spindle microtubules during mitosis. Non-motor proteins localize to distinct subcellular sites, such as kinetochores and centrosomes, during different phases of mitosis. They are responsible for linking spindle microtubules to the kinetochore to ensure proper chromosomal alignment during metaphase, and are required for centrosome maturation and separation. Acting together with motor proteins, the non-motor proteins thus enable the formation of the bipolar spindle with microtubules spanning from spindle poles to kinetochores and between spindle poles. At the spindle midzone, specific MAPs cause bundling of antiparallel microtubules that is a prerequisite for proper cell cleavage. Interestingly, the non-motor proteins are frequently overexpressed in different tumors. Among the anti-mitotic drugs currently in clinical use, drugs that target microtubules have been the most successful to date. An emerging class of potential chemotherapy drugs includes inhibitors of non-motor spindle proteins such as the Aurora A and B protein kinases and Polo-like kinase-1. Many non-motor microtubule associated proteins, including the KMN (KNL-1/Mis12 complex/Ndc80) and CPC (chromosome passenger complex) networks of interacting proteins, are potentially suitable as drug targets in mitosis. Drug screens must be designed to identify compounds that modify well-defined activities of the target proteins, and to interfere with completion of mitosis in tumor cells. Combination therapy, involving DNA damage followed by a mitotic second trap using drugs that target non-motor spindle proteins, could be a valuable approach when tumor cell response is differentially insensitive to DNA damage. In this chapter we describe important non-motor proteins that may serve as potential therapeutic targets.

Keywords

Mitotic Spindle Aurora Kinase Spindle Pole Spindle Assembly Spindle Assembly Checkpoint 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Supported by NIH grants R01GM068107 and R01GM088716 (R.L.M.)

References

  1. 1.
    Compton DA (2000) Spindle assembly in animal cells. Annu Rev Biochem 69:95–114PubMedGoogle Scholar
  2. 2.
    Maiato H, Rieder CL, Khodjakov A (2004) Kinetochore-driven formation of kinetochore fibers contributes to spindle assembly during animal mitosis. J Cell Biol 167(5):831–840PubMedCentralPubMedGoogle Scholar
  3. 3.
    Fant X, Merdes A, Haren L (2004) Cell and molecular biology of spindle poles and NuMA. Int Rev Cytol 238:1–57PubMedGoogle Scholar
  4. 4.
    Mollinari C et al (2002) PRC1 is a microtubule binding and bundling protein essential to maintain the mitotic spindle midzone. J Cell Biol 157(7):1175–1186PubMedCentralPubMedGoogle Scholar
  5. 5.
    Wong J et al (2007) A protein interaction map of the mitotic spindle. Mol Biol Cell 18(10):3800–3809PubMedCentralPubMedGoogle Scholar
  6. 6.
    Rojas AM et al (2012) Uncovering the molecular machinery of the human spindle–an integration of wet and dry systems biology. PLoS One 7(3):e31813PubMedCentralPubMedGoogle Scholar
  7. 7.
    Margolis RL, Wilson L, Keifer BI (1978) Mitotic mechanism based on intrinsic microtubule behaviour. Nature 272(5652):450–452PubMedGoogle Scholar
  8. 8.
    Witt PL, Ris H, Borisy GG (1980) Origin of kinetochore microtubules in Chinese hamster ovary cells. Chromosoma 81(3):483–505PubMedGoogle Scholar
  9. 9.
    Khodjakov A, Copenagle L, Gordon MB, Compton DA, Kapoor TM (2003) Minus-end capture of preformed kinetochore fibers contributes to spindle morphogenesis. J Cell Biol 160(5):671–683PubMedCentralPubMedGoogle Scholar
  10. 10.
    Khodjakov A, Cole RW, Oakley BR, Rieder CL (2000) Centrosome-independent mitotic spindle formation in vertebrates. Curr Biol 10(2):59–67PubMedGoogle Scholar
  11. 11.
    Hinchcliffe EH, Miller FJ, Cham M, Khodjakov A, Sluder G (2001) Requirement of a centrosomal activity for cell cycle progression through G1 into S phase. Science 291(5508):1547–1550PubMedGoogle Scholar
  12. 12.
    Sawin KE, Mitchison TJ (1994) Microtubule flux in mitosis is independent of chromosomes, centrosomes, and antiparallel microtubules. Mol Biol Cell 5(2):217–226PubMedCentralPubMedGoogle Scholar
  13. 13.
    Carazo-Salas RE et al (1999) Generation of GTP-bound Ran by RCC1 is required for chromatin-induced mitotic spindle formation. Nature 400(6740):178–181PubMedGoogle Scholar
  14. 14.
    Tsai MY et al (2003) A Ran signalling pathway mediated by the mitotic kinase Aurora A in spindle assembly. Nat Cell Biol 5(3):242–248PubMedGoogle Scholar
  15. 15.
    O’Connell CB, Loncarek J, Kalab P, Khodjakov A (2009) Relative contributions of chromatin and kinetochores to mitotic spindle assembly. J Cell Biol 187(1):43–51PubMedCentralPubMedGoogle Scholar
  16. 16.
    Kalab P, Weis K, Heald R (2002) Visualization of a Ran-GTP gradient in interphase and mitotic Xenopus egg extracts. Science 295(5564):2452–2456PubMedGoogle Scholar
  17. 17.
    Heald R et al (1996) Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts. Nature 382(6590):420–425PubMedGoogle Scholar
  18. 18.
    Maresca TJ et al (2009) Spindle assembly in the absence of a RanGTP gradient requires localized CPC activity. Curr Biol 19(14):1210–1215PubMedCentralPubMedGoogle Scholar
  19. 19.
    Mitchison TJ, Salmon ED (1992) Poleward kinetochore fiber movement occurs during both metaphase and anaphase-A in newt lung cell mitosis. J Cell Biol 119(3):569–582PubMedGoogle Scholar
  20. 20.
    Maddox P, Desai A, Oegema K, Mitchison TJ, Salmon ED (2002) Poleward microtubule flux is a major component of spindle dynamics and anaphase a in mitotic Drosophila embryos. Curr Biol 12(19):1670–1674PubMedGoogle Scholar
  21. 21.
    Grill SW, Howard J, Schaffer E, Stelzer EH, Hyman AA (2003) The distribution of active force generators controls mitotic spindle position. Science 301(5632):518–521PubMedGoogle Scholar
  22. 22.
    Kotak S, Gonczy P (2013) Mechanisms of spindle positioning: cortical force generators in the limelight. Curr Opin Cell Biol 25(6):741–748PubMedGoogle Scholar
  23. 23.
    Woodard GE et al (2010) Ric-8A and Gi alpha recruit LGN, NuMA, and dynein to the cell cortex to help orient the mitotic spindle. Mol Cell Biol 30(14):3519–3530PubMedCentralPubMedGoogle Scholar
  24. 24.
    Laan L et al (2012) Cortical dynein controls microtubule dynamics to generate pulling forces that position microtubule asters. Cell 148(3):502–514PubMedCentralPubMedGoogle Scholar
  25. 25.
    Canman JC et al (2003) Determining the position of the cell division plane. Nature 424(6952):1074–1078PubMedGoogle Scholar
  26. 26.
    Skoufias DA, Indorato RL, Lacroix F, Panopoulos A, Margolis RL (2007) Mitosis persists in the absence of Cdk1 activity when proteolysis or protein phosphatase activity is suppressed. J Cell Biol 179(4):671–685PubMedCentralPubMedGoogle Scholar
  27. 27.
    Zhou H et al (1998) Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nat Genet 20(2):189–193PubMedGoogle Scholar
  28. 28.
    Tanaka T et al (1999) Centrosomal kinase AIK1 is overexpressed in invasive ductal carcinoma of the breast. Cancer Res 59(9):2041–2044PubMedGoogle Scholar
  29. 29.
    Warner SL et al (2006) Comparing Aurora A and Aurora B as molecular targets for growth inhibition of pancreatic cancer cells. Mol Cancer Ther 5(10):2450–2458PubMedGoogle Scholar
  30. 30.
    Araki K, Nozaki K, Ueba T, Tatsuka M, Hashimoto N (2004) High expression of Aurora-B/Aurora and Ipll-like midbody-associated protein (AIM-1) in astrocytomas. J Neurooncol 67(1–2):53–64PubMedGoogle Scholar
  31. 31.
    Smith SL et al (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(6):719–729PubMedCentralPubMedGoogle Scholar
  32. 32.
    Eckerdt F et al (2005) Polo-like kinase 1-mediated phosphorylation stabilizes Pin1 by inhibiting its ubiquitination in human cells. J Biol Chem 280(44):36575–36583PubMedGoogle Scholar
  33. 33.
    Strebhardt K, Ullrich A (2006) Targeting polo-like kinase 1 for cancer therapy. Nat Rev Cancer 6(4):321–330PubMedGoogle Scholar
  34. 34.
    Keen N, Taylor S (2004) Aurora-kinase inhibitors as anticancer agents. Nat Rev Cancer 4(12):927–936PubMedGoogle Scholar
  35. 35.
    Malumbres M, Barbacid M (2009) Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 9(3):153–166PubMedGoogle Scholar
  36. 36.
    Bischoff JR, Plowman GD (1999) The Aurora/Ipl1p kinase family: regulators of chromosome segregation and cytokinesis. Trends Cell Biol 9(11):454–459PubMedGoogle Scholar
  37. 37.
    Giet R, Prigent C (1999) Aurora/Ipl1p-related kinases, a new oncogenic family of mitotic serine-threonine kinases. J Cell Sci 112(Pt 21):3591–3601PubMedGoogle Scholar
  38. 38.
    Giet R, Petretti C, Prigent C (2005) Aurora kinases, aneuploidy and cancer, a coincidence or a real link? Trends Cell Biol 15(5):241–250PubMedGoogle Scholar
  39. 39.
    Ruchaud S, Carmena M, Earnshaw WC (2007) Chromosomal passengers: conducting cell division. Nature reviews. Mol Cell Biol 8(10):798–812Google Scholar
  40. 40.
    Kufer TA et al (2002) Human TPX2 is required for targeting Aurora-A kinase to the spindle. J Cell Biol 158(4):617–623PubMedCentralPubMedGoogle Scholar
  41. 41.
    Hirota T et al (2003) Aurora-A and an interacting activator, the LIM protein Ajuba, are required for mitotic commitment in human cells. Cell 114(5):585–598PubMedGoogle Scholar
  42. 42.
    Hannak E, Kirkham M, Hyman AA, Oegema K (2001) Aurora-A kinase is required for centrosome maturation in Caenorhabditis elegans. J Cell Biol 155(7):1109–1116PubMedCentralPubMedGoogle Scholar
  43. 43.
    Anand S, Penrhyn-Lowe S, Venkitaraman AR (2003) AURORA-A amplification overrides the mitotic spindle assembly checkpoint, inducing resistance to Taxol. Cancer Cell 3(1):51–62PubMedGoogle Scholar
  44. 44.
    Macurek L et al (2008) Regulation of microtubule nucleation from membranes by complexes of membrane-bound gamma-tubulin with Fyn kinase and phosphoinositide 3-kinase. Biochem J 416(3):421–430PubMedGoogle Scholar
  45. 45.
    Dutertre S, Descamps S, Prigent C (2002) On the role of aurora-A in centrosome function. Oncogene 21(40):6175–6183PubMedGoogle Scholar
  46. 46.
    Meraldi P, Honda R, Nigg EA (2002) Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53-/- cells. EMBO J 21(4):483–492PubMedCentralPubMedGoogle Scholar
  47. 47.
    Cooke CA, Heck MM, Earnshaw WC (1987) The inner centromere protein (INCENP) antigens: movement from inner centromere to midbody during mitosis. J Cell Biol 105(5):2053–2067PubMedGoogle Scholar
  48. 48.
    Adams RR et al (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(17):1075–1078PubMedGoogle Scholar
  49. 49.
    Bishop JD, Schumacher JM (2002) Phosphorylation of the carboxyl terminus of inner centromere protein (INCENP) by the Aurora B kinase stimulates Aurora B kinase activity. J Biol Chem 277(31):27577–27580PubMedCentralPubMedGoogle Scholar
  50. 50.
    Honda R, Korner R, Nigg EA (2003) Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis. Mol Biol Cell 14(8):3325–3341PubMedCentralPubMedGoogle Scholar
  51. 51.
    Sessa F et al (2005) Mechanism of Aurora B activation by INCENP and inhibition by hesperadin. Mol Cell 18(3):379–391PubMedGoogle Scholar
  52. 52.
    Carmena M, Earnshaw WC (2003) The cellular geography of aurora kinases. Nat Rev Mol Cell Biol 4(11):842–854PubMedGoogle Scholar
  53. 53.
    Andrews PD et al (2004) Aurora B regulates MCAK at the mitotic centromere. Dev Cell 6(2):253–268PubMedGoogle Scholar
  54. 54.
    Jeyaprakash AA et al (2007) Structure of a Survivin-Borealin-INCENP core complex reveals how chromosomal passengers travel together. Cell 131(2):271–285PubMedGoogle Scholar
  55. 55.
    Jelluma N et al (2008) Mps1 phosphorylates Borealin to control Aurora B activity and chromosome alignment. Cell 132(2):233–246PubMedGoogle Scholar
  56. 56.
    Ciferri C et al (2008) Implications for kinetochore-microtubule attachment from the structure of an engineered Ndc80 complex. Cell 133(3):427–439PubMedGoogle Scholar
  57. 57.
    Fuller BG et al (2008) Midzone activation of aurora B in anaphase produces an intracellular phosphorylation gradient. Nature 453(7198):1132–1136PubMedCentralPubMedGoogle Scholar
  58. 58.
    Tien AC et al (2004) Identification of the substrates and interaction proteins of aurora kinases from a protein-protein interaction model. Mol Cell Proteomics 3(1):93–104PubMedGoogle Scholar
  59. 59.
    Meraldi P, Honda R, Nigg EA (2004) Aurora kinases link chromosome segregation and cell division to cancer susceptibility. Curr Opin Genet Dev 14(1):29–36PubMedGoogle Scholar
  60. 60.
    Ohashi S et al (2006) Phospho-regulation of human protein kinase Aurora-A: analysis using anti-phospho-Thr288 monoclonal antibodies. Oncogene 25(59):7691–7702PubMedGoogle Scholar
  61. 61.
    Fu J, Bian M, Jiang Q, Zhang C (2007) Roles of Aurora kinases in mitosis and tumorigenesis. Mol Cancer Res 5(1):1–10PubMedGoogle Scholar
  62. 62.
    Macurek L et al (2008) Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery. Nature 455(7209):119–123PubMedGoogle Scholar
  63. 63.
    Kunitoku N et al (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(6):853–864PubMedGoogle Scholar
  64. 64.
    Hans F, Skoufias DA, Dimitrov S, Margolis RL (2009) Molecular distinctions between Aurora A and B: a single residue change transforms Aurora A into correctly localized and functional Aurora B. Mol Biol Cell 20(15):3491–3502PubMedCentralPubMedGoogle Scholar
  65. 65.
    Lindon C, Pines J (2004) Ordered proteolysis in anaphase inactivates Plk1 to contribute to proper mitotic exit in human cells. J Cell Biol 164(2):233–241PubMedCentralPubMedGoogle Scholar
  66. 66.
    Crane R, Kloepfer A, Ruderman JV (2004) Requirements for the destruction of human Aurora-A. J Cell Sci 117(Pt 25):5975–5983PubMedGoogle Scholar
  67. 67.
    Petronczki M, Lenart P, Peters JM (2008) Polo on the rise-from mitotic entry to cytokinesis with Plk1. Dev Cell 14(5):646–659PubMedGoogle Scholar
  68. 68.
    van Vugt MA, Medema RH (2005) Getting in and out of mitosis with Polo-like kinase-1. Oncogene 24(17):2844–2859PubMedGoogle Scholar
  69. 69.
    Schatten H (2008) The mammalian centrosome and its functional significance. Histochem Cell Biol 129(6):667–686PubMedCentralPubMedGoogle Scholar
  70. 70.
    Neef R et al (2007) Choice of Plk1 docking partners during mitosis and cytokinesis is controlled by the activation state of Cdk1. Nat Cell Biol 9(4):436–444PubMedGoogle Scholar
  71. 71.
    Hu CK, Ozlu N, Coughlin M, Steen JJ, Mitchison TJ (2012) Plk1 negatively regulates PRC1 to prevent premature midzone formation before cytokinesis. Mol Biol Cell 23(14):2702–2711PubMedCentralPubMedGoogle Scholar
  72. 72.
    Petronczki M, Glotzer M, Kraut N, Peters JM (2007) Polo-like kinase 1 triggers the initiation of cytokinesis in human cells by promoting recruitment of the RhoGEF Ect2 to the central spindle. Dev Cell 12(5):713–725PubMedGoogle Scholar
  73. 73.
    Fourest-Lieuvin A et al (2006) Microtubule regulation in mitosis: tubulin phosphorylation by the cyclin-dependent kinase Cdk1. Mol Biol Cell 17(3):1041–1050PubMedCentralPubMedGoogle Scholar
  74. 74.
    Blethrow JD, Glavy JS, Morgan DO, Shokat KM (2008) Covalent capture of kinase-specific phosphopeptides reveals Cdk1-cyclin B substrates. Proc Natl Acad Sci U S A 105(5):1442–1447PubMedCentralPubMedGoogle Scholar
  75. 75.
    Wheatley SP et al (1997) CDK1 inactivation regulates anaphase spindle dynamics and cytokinesis in vivo. J Cell Biol 138(2):385–393PubMedCentralPubMedGoogle Scholar
  76. 76.
    Dephoure N et al (2008) A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A 105(31):10762–10767PubMedCentralPubMedGoogle Scholar
  77. 77.
    Nousiainen M, Sillje HH, Sauer G, Nigg EA, Korner R (2006) Phosphoproteome analysis of the human mitotic spindle. Proc Natl Acad Sci U S A 103(14):5391–5396PubMedCentralPubMedGoogle Scholar
  78. 78.
    Barra HS, Arce CA, Argarana CE (1988) Posttranslational tyrosination/detyrosination of tubulin. Mol Neurobiol 2(2):133–153PubMedGoogle Scholar
  79. 79.
    Sahab ZJ et al (2011) Tumor suppressor RARRES1 interacts with cytoplasmic carboxypeptidase AGBL2 to regulate the alpha-tubulin tyrosination cycle. Cancer Res 71(4):1219–1228PubMedCentralPubMedGoogle Scholar
  80. 80.
    Bieling P et al (2008) CLIP-170 tracks growing microtubule ends by dynamically recognizing composite EB1/tubulin-binding sites. J Cell Biol 183(7):1223–1233PubMedCentralPubMedGoogle Scholar
  81. 81.
    Lansbergen G, Akhmanova A (2006) Microtubule plus end: a hub of cellular activities. Traffic 7(5):499–507PubMedGoogle Scholar
  82. 82.
    Akhmanova A, Steinmetz MO (2008) Tracking the ends: a dynamic protein network controls the fate of microtubule tips. Nat Rev Mol Cell Biol 9(4):309–322PubMedGoogle Scholar
  83. 83.
    Lafanechere L et al (1998) Suppression of tubulin tyrosine ligase during tumor growth. J Cell Sci 111(Pt 2):171–181PubMedGoogle Scholar
  84. 84.
    Mialhe A et al (2001) Tubulin detyrosination is a frequent occurrence in breast cancers of poor prognosis. Cancer Res 61(13):5024–5027PubMedGoogle Scholar
  85. 85.
    Peris L et al (2006) Tubulin tyrosination is a major factor affecting the recruitment of CAP-Gly proteins at microtubule plus ends. J Cell Biol 174(6):839–849PubMedCentralPubMedGoogle Scholar
  86. 86.
    Mitchison TJ et al (2004) Bipolarization and poleward flux correlate during Xenopus extract spindle assembly. Mol Biol Cell 15(12):5603–5615PubMedCentralPubMedGoogle Scholar
  87. 87.
    Pedrotti B, Ulloa L, Avila J, Islam K (1996) Characterization of microtubule-associated protein MAP1B: phosphorylation state, light chains, and binding to microtubules. Biochemistry 35(9):3016–3023PubMedGoogle Scholar
  88. 88.
    Valiron O, Caudron N, Job D (2001) Microtubule dynamics. Cell Mol Life Sci 58(14):2069–2084PubMedGoogle Scholar
  89. 89.
    Chien CL, Lu KS, Lin YS, Hsieh CJ, Hirokawa N (2005) The functional cooperation of MAP1A heavy chain and light chain 2 in the binding of microtubules. Exp Cell Res 308(2):446–458PubMedGoogle Scholar
  90. 90.
    Curmi PA et al (1999) Stathmin and its phosphoprotein family: general properties, biochemical and functional interaction with tubulin. Cell Struct Funct 24(5):345–357PubMedGoogle Scholar
  91. 91.
    Manna T, Thrower D, Miller HP, Curmi P, Wilson L (2006) Stathmin strongly increases the minus end catastrophe frequency and induces rapid treadmilling of bovine brain microtubules at steady state in vitro. J Biol Chem 281(4):2071–2078PubMedGoogle Scholar
  92. 92.
    Walczak CE, Mitchison TJ, Desai A (1996) XKCM1: a Xenopus kinesin-related protein that regulates microtubule dynamics during mitotic spindle assembly. Cell 84(1):37–47PubMedGoogle Scholar
  93. 93.
    McNally FJ, Thomas S (1998) Katanin is responsible for the M-phase microtubule-severing activity in Xenopus eggs. Mol Biol Cell 9(7):1847–1861PubMedCentralPubMedGoogle Scholar
  94. 94.
    Tournebize R et al (2000) Control of microtubule dynamics by the antagonistic activities of XMAP215 and XKCM1 in Xenopus egg extracts. Nat Cell Biol 2(1):13–19PubMedGoogle Scholar
  95. 95.
    Dionne MA, Sanchez A, Compton DA (2000) ch-TOGp is required for microtubule aster formation in a mammalian mitotic extract. J Biol Chem 275(16):12346–12352PubMedGoogle Scholar
  96. 96.
    Cassimeris L, Morabito J (2004) TOGp, the human homolog of XMAP215/Dis1, is required for centrosome integrity, spindle pole organization, and bipolar spindle assembly. Mol Biol Cell 15(4):1580–1590PubMedCentralPubMedGoogle Scholar
  97. 97.
    Holmfeldt P, Stenmark S, Gullberg M (2004) Differential functional interplay of TOGp/XMAP215 and the KinI kinesin MCAK during interphase and mitosis. EMBO J 23(3):627–637PubMedCentralPubMedGoogle Scholar
  98. 98.
    Kinoshita K, Noetzel TL, Arnal I, Drechsel DN, Hyman AA (2006) Global and local control of microtubule destabilization promoted by a catastrophe kinesin MCAK/XKCM1. J Muscle Res Cell Motil 27(2):107–114PubMedGoogle Scholar
  99. 99.
    Kinoshita K, Habermann B, Hyman AA (2002) XMAP215: a key component of the dynamic microtubule cytoskeleton. Trends Cell Biol 12(6):267–273PubMedGoogle Scholar
  100. 100.
    Ookata K et al (1995) Cyclin B interaction with microtubule-associated protein 4 (MAP4) targets p34cdc2 kinase to microtubules and is a potential regulator of M-phase microtubule dynamics. J Cell Biol 128(5):849–862PubMedGoogle Scholar
  101. 101.
    Cassimeris L (1999) Accessory protein regulation of microtubule dynamics throughout the cell cycle. Curr Opin Cell Biol 11(1):134–141PubMedGoogle Scholar
  102. 102.
    Wu X, Xiang X, Hammer JA 3rd (2006) Motor proteins at the microtubule plus-end. Trends Cell Biol 16(3):135–143PubMedGoogle Scholar
  103. 103.
    Tirnauer JS, Canman JC, Salmon ED, Mitchison TJ (2002) EB1 targets to kinetochores with attached, polymerizing microtubules. Mol Biol Cell 13(12):4308–4316PubMedCentralPubMedGoogle Scholar
  104. 104.
    Galjart N (2005) CLIPs and CLASPs and cellular dynamics. Nat Rev Mol Cell Biol 6(6):487–498PubMedGoogle Scholar
  105. 105.
    Pabion M, Job D, Margolis RL (1984) Sliding of STOP proteins on microtubules. Biochemistry 23(26):6642–6648PubMedGoogle Scholar
  106. 106.
    Margolis RL, Wilson L (1981) Microtubule treadmills–possible molecular machinery. Nature 293(5835):705–711PubMedGoogle Scholar
  107. 107.
    Garel JR, Job D, Margolis RL (1987) Model of anaphase chromosome movement based on polymer-guided diffusion. Proc Natl Acad Sci U S A 84(11):3599–3603PubMedCentralPubMedGoogle Scholar
  108. 108.
    Rogers SL, Rogers GC, Sharp DJ, Vale RD (2002) Drosophila EB1 is important for proper assembly, dynamics, and positioning of the mitotic spindle. J Cell Biol 158(5):873–884PubMedCentralPubMedGoogle Scholar
  109. 109.
    Maiato H et al (2003) Human CLASP1 is an outer kinetochore component that regulates spindle microtubule dynamics. Cell 113(7):891–904PubMedGoogle Scholar
  110. 110.
    Reis R et al (2009) Dynein and mast/orbit/CLASP have antagonistic roles in regulating kinetochore-microtubule plus-end dynamics. J Cell Sci 122(Pt 14):2543–2553PubMedGoogle Scholar
  111. 111.
    Schuyler SC, Pellman D (2001) Microtubule “plus-end-tracking proteins”: the end is just the beginning. Cell 105(4):421–424PubMedGoogle Scholar
  112. 112.
    Maiato H, Sampaio P, Sunkel CE (2004) Microtubule-associated proteins and their essential roles during mitosis. Int Rev Cytol 241:53–153PubMedGoogle Scholar
  113. 113.
    Palmer DK, O’Day K, Trong HL, Charbonneau H, Margolis RL (1991) Purification of the centromere-specific protein CENP-A and demonstration that it is a distinctive histone. Proc Natl Acad Sci U S A 88(9):3734–3738PubMedCentralPubMedGoogle Scholar
  114. 114.
    Kline-Smith SL, Sandall S, Desai A (2005) Kinetochore-spindle microtubule interactions during mitosis. Curr Opin Cell Biol 17(1):35–46PubMedGoogle Scholar
  115. 115.
    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):1763–1768PubMedGoogle Scholar
  116. 116.
    Cheeseman IM, Chappie JS, Wilson-Kubalek EM, Desai A (2006) The conserved KMN network constitutes the core microtubule-binding site of the kinetochore. Cell 127(5):983–997PubMedGoogle Scholar
  117. 117.
    Tanaka TU, Desai A (2008) Kinetochore-microtubule interactions: the means to the end. Curr Opin Cell Biol 20(1):53–63PubMedCentralPubMedGoogle Scholar
  118. 118.
    DeLuca JG et al (2006) Kinetochore microtubule dynamics and attachment stability are regulated by Hec1. Cell 127(5):969–982PubMedGoogle Scholar
  119. 119.
    Maiato H, DeLuca J, Salmon ED, Earnshaw WC (2004) The dynamic kinetochore-microtubule interface. J Cell Sci 117(Pt 23):5461–5477PubMedGoogle Scholar
  120. 120.
    Chan GK, Liu ST, Yen TJ (2005) Kinetochore structure and function. Trends Cell Biol 15(11):589–598PubMedGoogle Scholar
  121. 121.
    Wan X et al (2009) Protein architecture of the human kinetochore microtubule attachment site. Cell 137(4):672–684PubMedCentralPubMedGoogle Scholar
  122. 122.
    Karess R (2005) Rod-Zw10-Zwilch: a key player in the spindle checkpoint. Trends Cell Biol 15(7):386–392PubMedGoogle Scholar
  123. 123.
    Griffis ER, Stuurman N, Vale RD (2007) Spindly, a novel protein essential for silencing the spindle assembly checkpoint, recruits dynein to the kinetochore. J Cell Biol 177(6):1005–1015PubMedCentralPubMedGoogle Scholar
  124. 124.
    Chan YW et al (2009) Mitotic control of kinetochore-associated dynein and spindle orientation by human spindly. J Cell Biol 185(5):859–874PubMedCentralPubMedGoogle Scholar
  125. 125.
    Maure JF et al (2011) The Ndc80 loop region facilitates formation of kinetochore attachment to the dynamic microtubule plus end. Curr Biol 21(3):207–213PubMedCentralPubMedGoogle Scholar
  126. 126.
    Tanaka K, Kitamura E, Kitamura Y, Tanaka TU (2007) Molecular mechanisms of microtubule-dependent kinetochore transport toward spindle poles. J Cell Biol 178(2):269–281PubMedCentralPubMedGoogle Scholar
  127. 127.
    Miranda JJ, De Wulf P, Sorger PK, Harrison SC (2005) The yeast DASH complex forms closed rings on microtubules. Nat Struct Mol Biol 12(2):138–143PubMedGoogle Scholar
  128. 128.
    Nogales E, Ramey VH (2009) Structure-function insights into the yeast Dam1 kinetochore complex. J Cell Sci 122(Pt 21):3831–3836PubMedCentralPubMedGoogle Scholar
  129. 129.
    Mollinari C et al (2003) The mammalian passenger protein TD-60 is an RCC1 family member with an essential role in prometaphase to metaphase progression. Dev Cell 5(2):295–307PubMedGoogle Scholar
  130. 130.
    Kotwaliwale C, Biggins S (2006) Microtubule capture: a concerted effort. Cell 127(6):1105–1108PubMedGoogle Scholar
  131. 131.
    Rosasco-Nitcher SE, Lan W, Khorasanizadeh S, Stukenberg PT (2008) Centromeric Aurora-B activation requires TD-60, microtubules, and substrate priming phosphorylation. Science 319(5862):469–472PubMedGoogle Scholar
  132. 132.
    Wang F et al (2010) Histone H3 Thr-3 phosphorylation by Haspin positions Aurora B at centromeres in mitosis. Science 330(6001):231–235PubMedCentralPubMedGoogle Scholar
  133. 133.
    Sampath SC et al (2004) The chromosomal passenger complex is required for chromatin-induced microtubule stabilization and spindle assembly. Cell 118(2):187–202PubMedGoogle Scholar
  134. 134.
    Emanuele MJ et al (2008) Aurora B kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly. J Cell Biol 181(2):241–254PubMedCentralPubMedGoogle Scholar
  135. 135.
    Skoufias DA, Andreassen PR, Lacroix FB, Wilson L, Margolis RL (2001) Mammalian mad2 and bub1/bubR1 recognize distinct spindle-attachment and kinetochore-tension checkpoints. Proc Natl Acad Sci U S A 98(8):4492–4497PubMedCentralPubMedGoogle Scholar
  136. 136.
    Tanaka TU et al (2002) Evidence that the Ipl1-Sli15 (Aurora kinase-INCENP) complex promotes chromosome bi-orientation by altering kinetochore-spindle pole connections. Cell 108(3):317–329PubMedGoogle Scholar
  137. 137.
    Knowlton AL, Lan W, Stukenberg PT (2006) Aurora B is enriched at merotelic attachment sites, where it regulates MCAK. Curr Biol 16(17):1705–1710PubMedGoogle Scholar
  138. 138.
    Takai N, Hamanaka R, Yoshimatsu J, Miyakawa I (2005) Polo-like kinases (Plks) and cancer. Oncogene 24(2):287–291PubMedGoogle Scholar
  139. 139.
    Negrini S, Gorgoulis VG, Halazonetis TD (2010) Genomic instability–an evolving hallmark of cancer. Nat Rev Mol Cell Biol 11(3):220–228PubMedGoogle Scholar
  140. 140.
    Cimini D, Wan X, Hirel CB, Salmon ED (2006) Aurora kinase promotes turnover of kinetochore microtubules to reduce chromosome segregation errors. Curr Biol 16(17):1711–1718PubMedGoogle Scholar
  141. 141.
    Gascoigne KE, Cheeseman IM (2011) Kinetochore assembly: if you build it, they will come. Curr Opin Cell Biol 23(1):102–108PubMedCentralPubMedGoogle Scholar
  142. 142.
    Merdes A, Heald R, Samejima K, Earnshaw WC, Cleveland DW (2000) Formation of spindle poles by dynein/dynactin-dependent transport of NuMA. J Cell Biol 149(4):851–862PubMedCentralPubMedGoogle Scholar
  143. 143.
    Merdes A, Ramyar K, Vechio JD, Cleveland DW (1996) A complex of NuMA and cytoplasmic dynein is essential for mitotic spindle assembly. Cell 87(3):447–458PubMedGoogle Scholar
  144. 144.
    Garrett S, Auer K, Compton DA, Kapoor TM (2002) hTPX2 is required for normal spindle morphology and centrosome integrity during vertebrate cell division. Curr Biol 12(23):2055–2059PubMedGoogle Scholar
  145. 145.
    Wittmann T, Wilm M, Karsenti E, Vernos I (2000) TPX2, A novel Xenopus MAP involved in spindle pole organization. J Cell Biol 149(7):1405–1418PubMedCentralPubMedGoogle Scholar
  146. 146.
    Eyers PA, Maller JL (2004) Regulation of Xenopus Aurora A activation by TPX2. J Biol Chem 279(10):9008–9015PubMedGoogle Scholar
  147. 147.
    Gruss OJ, Vernos I (2004) The mechanism of spindle assembly: functions of Ran and its target TPX2. J Cell Biol 166(7):949–955PubMedCentralPubMedGoogle Scholar
  148. 148.
    Kufer TA, Nigg EA, Sillje HH (2003) Regulation of Aurora-A kinase on the mitotic spindle. Chromosoma 112(4):159–163PubMedGoogle Scholar
  149. 149.
    Hood FE, Royle SJ (2011) Pulling it together: the mitotic function of TACC3. Bioarchitecture 1(3):105–109PubMedCentralPubMedGoogle Scholar
  150. 150.
    Peset I et al (2005) Function and regulation of Maskin, a TACC family protein, in microtubule growth during mitosis. J Cell Biol 170(7):1057–1066PubMedCentralPubMedGoogle Scholar
  151. 151.
    Nachury MV et al (2001) Importin beta is a mitotic target of the small GTPase Ran in spindle assembly. Cell 104(1):95–106PubMedGoogle Scholar
  152. 152.
    Taylor S, Peters JM (2008) Polo and Aurora kinases: lessons derived from chemical biology. Curr Opin Cell Biol 20(1):77–84PubMedGoogle Scholar
  153. 153.
    Lane HA, Nigg EA (1996) Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in the functional maturation of mitotic centrosomes. J Cell Biol 135(6 Pt 2):1701–1713PubMedGoogle Scholar
  154. 154.
    Berdnik D, Knoblich JA (2002) Drosophila Aurora-A is required for centrosome maturation and actin-dependent asymmetric protein localization during mitosis. Curr Biol 12(8):640–647PubMedGoogle Scholar
  155. 155.
    Tsai MY, Zheng Y (2005) Aurora A kinase-coated beads function as microtubule-organizing centers and enhance RanGTP-induced spindle assembly. Curr Biol 15(23):2156–2163PubMedGoogle Scholar
  156. 156.
    Barr AR, Gergely F (2007) Aurora-A: the maker and breaker of spindle poles. J Cell Sci 120(Pt 17):2987–2996PubMedGoogle Scholar
  157. 157.
    Pihan GA (2013) Centrosome dysfunction contributes to chromosome instability, chromoanagenesis, and genome reprograming in cancer. Front Oncol 3:277PubMedCentralPubMedGoogle Scholar
  158. 158.
    Hayward DG et al (2004) The centrosomal kinase Nek2 displays elevated levels of protein expression in human breast cancer. Cancer Res 64(20):7370–7376PubMedGoogle Scholar
  159. 159.
    Cappello P et al (2014) Role of Nek2 on centrosome duplication and aneuploidy in breast cancer cells. Oncogene 33:2375–2384PubMedGoogle Scholar
  160. 160.
    Takahashi Y et al (2014) Up-regulation of NEK2 by microRNA-128 methylation is associated with poor prognosis in colorectal cancer. Ann Surg Oncol 21:205–212PubMedGoogle Scholar
  161. 161.
    Fry AM, Schultz SJ, Bartek J, Nigg EA (1995) Substrate specificity and cell cycle regulation of the Nek2 protein kinase, a potential human homolog of the mitotic regulator NIMA of Aspergillus nidulans. J Biol Chem 270(21):12899–12905PubMedGoogle Scholar
  162. 162.
    Mi J, Guo C, Brautigan DL, Larner JM (2007) Protein phosphatase-1alpha regulates centrosome splitting through Nek2. Cancer Res 67(3):1082–1089PubMedGoogle Scholar
  163. 163.
    Bieling P, Telley IA, Surrey T (2010) A minimal midzone protein module controls formation and length of antiparallel microtubule overlaps. Cell 142(3):420–432PubMedGoogle Scholar
  164. 164.
    Subramanian R et al (2010) Insights into antiparallel microtubule crosslinking by PRC1, a conserved nonmotor microtubule binding protein. Cell 142(3):433–443PubMedCentralPubMedGoogle Scholar
  165. 165.
    Kurasawa Y, Earnshaw WC, Mochizuki Y, Dohmae N, Todokoro K (2004) Essential roles of KIF4 and its binding partner PRC1 in organized central spindle midzone formation. EMBO J 23(16):3237–3248PubMedCentralPubMedGoogle Scholar
  166. 166.
    Shrestha S, Wilmeth LJ, Eyer J, Shuster CB (2012) PRC1 controls spindle polarization and recruitment of cytokinetic factors during monopolar cytokinesis. Mol Biol Cell 23(7):1196–1207PubMedCentralPubMedGoogle Scholar
  167. 167.
    Mollinari C et al (2005) Ablation of PRC1 by small interfering RNA demonstrates that cytokinetic abscission requires a central spindle bundle in mammalian cells, whereas completion of furrowing does not. Mol Biol Cell 16(3):1043–1055PubMedCentralPubMedGoogle Scholar
  168. 168.
    Floyd S, Pines J, Lindon C (2008) APC/C Cdh1 targets aurora kinase to control reorganization of the mitotic spindle at anaphase. Curr Biol 18(21):1649–1658PubMedGoogle Scholar
  169. 169.
    Agromayor M, Martin-Serrano J (2013) Knowing when to cut and run: mechanisms that control cytokinetic abscission. Trends Cell Biol 23(9):433–441PubMedGoogle Scholar
  170. 170.
    Jordan MA, Wilson L (2004) Microtubules as a target for anticancer drugs. Nat Rev Cancer 4(4):253–265PubMedGoogle Scholar
  171. 171.
    Yared JA, Tkaczuk KH (2012) Update on taxane development: new analogs and new formulations. Drug Des Devel Ther 6:371–384PubMedCentralPubMedGoogle Scholar
  172. 172.
    Dumontet C, Jordan MA, Lee FF (2009) Ixabepilone: targeting betaIII-tubulin expression in taxane-resistant malignancies. Mol Cancer Ther 8(1):17–25PubMedGoogle Scholar
  173. 173.
    Okouneva T, Azarenko O, Wilson L, Littlefield BA, Jordan MA (2008) Inhibition of centromere dynamics by eribulin (E7389) during mitotic metaphase. Mol Cancer Ther 7(7):2003–2011PubMedCentralPubMedGoogle Scholar
  174. 174.
    McInnes C, Mezna M, Fischer PM (2005) Progress in the discovery of polo-like kinase inhibitors. Curr Top Med Chem 5(2):181–197PubMedGoogle Scholar
  175. 175.
    Vader G, Lens SM (2008) The Aurora kinase family in cell division and cancer. Biochim Biophys Acta 1786(1):60–72PubMedGoogle Scholar
  176. 176.
    Smith MR et al (1997) Malignant transformation of mammalian cells initiated by constitutive expression of the polo-like kinase. Biochem Biophys Res Commun 234(2):397–405PubMedGoogle Scholar
  177. 177.
    Agnese V et al (2007) The role of Aurora-A inhibitors in cancer therapy. Ann Oncol 18(Suppl 6):vi47–vi52PubMedGoogle Scholar
  178. 178.
    Marumoto T, Zhang D, Saya H (2005) Aurora-A – a guardian of poles. Nat Rev Cancer 5(1):42–50PubMedGoogle Scholar
  179. 179.
    Yang H et al (2005) Mitotic requirement for aurora A kinase is bypassed in the absence of aurora B kinase. FEBS Lett 579(16):3385–3391PubMedGoogle Scholar
  180. 180.
    Shimomura T et al (2010) MK-5108, a highly selective Aurora-A kinase inhibitor, shows antitumor activity alone and in combination with docetaxel. Mol Cancer Ther 9(1):157–166PubMedGoogle Scholar
  181. 181.
    Hauf S et al (2003) The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint. J Cell Biol 161(2):281–294PubMedCentralPubMedGoogle Scholar
  182. 182.
    Ditchfield C et al (2003) Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. J Cell Biol 161(2):267–280PubMedCentralPubMedGoogle Scholar
  183. 183.
    Marzo I, Naval J (2013) Antimitotic drugs in cancer chemotherapy: promises and pitfalls. Biochem Pharmacol 86(6):703–710PubMedGoogle Scholar
  184. 184.
    Medema RH, Lin CC, Yang JC (2011) Polo-like kinase 1 inhibitors and their potential role in anticancer therapy, with a focus on NSCLC. Clin Cancer Res 17(20):6459–6466PubMedGoogle Scholar
  185. 185.
    Sumara I et al (2004) Roles of polo-like kinase 1 in the assembly of functional mitotic spindles. Curr Biol 14(19):1712–1722PubMedGoogle Scholar
  186. 186.
    Kaestner P, Bastians H (2010) Mitotic drug targets. J Cell Biochem 111(2):258–265PubMedGoogle Scholar
  187. 187.
    Gleixner KV et al (2010) Polo-like kinase 1 (Plk1) as a novel drug target in chronic myeloid leukemia: overriding imatinib resistance with the Plk1 inhibitor BI 2536. Cancer Res 70(4):1513–1523PubMedGoogle Scholar
  188. 188.
    Wilkinson RW et al (2007) AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosis. Clin Cancer Res 13(12):3682–3688PubMedGoogle Scholar
  189. 189.
    Hikichi Y et al (2012) TAK-960, a novel, orally available, selective inhibitor of polo-like kinase 1, shows broad-spectrum preclinical antitumor activity in multiple dosing regimens. Mol Cancer Ther 11(3):700–709PubMedGoogle Scholar
  190. 190.
    Wheatley SP, McNeish IA (2005) Survivin: a protein with dual roles in mitosis and apoptosis. Int Rev Cytol 247:35–88PubMedGoogle Scholar
  191. 191.
    Tao YF et al (2012) Survivin selective inhibitor YM155 induce apoptosis in SK-NEP-1 Wilms tumor cells. BMC Cancer 12:619PubMedCentralPubMedGoogle Scholar
  192. 192.
    Kelly RJ et al (2013) A phase I/II study of sepantronium bromide (YM155, survivin suppressor) with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer. Ann Oncol 24(10):2601–2606PubMedCentralPubMedGoogle Scholar
  193. 193.
    Berezov A et al (2012) Disabling the mitotic spindle and tumor growth by targeting a cavity-induced allosteric site of survivin. Oncogene 31(15):1938–1948PubMedCentralPubMedGoogle Scholar
  194. 194.
    Yue Z et al (2008) Deconstructing Survivin: comprehensive genetic analysis of Survivin function by conditional knockout in a vertebrate cell line. J Cell Biol 183(2):279–296PubMedCentralPubMedGoogle Scholar
  195. 195.
    Shi J, Orth JD, Mitchison T (2008) Cell type variation in responses to antimitotic drugs that target microtubules and kinesin-5. Cancer Res 68(9):3269–3276PubMedGoogle Scholar
  196. 196.
    Synold TW, Dussault I, Forman BM (2001) The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nat Med 7(5):584–590PubMedGoogle Scholar
  197. 197.
    Degenhardt Y et al (2010) Sensitivity of cancer cells to Plk1 inhibitor GSK461364A is associated with loss of p53 function and chromosome instability. Mol Cancer Ther 9(7):2079–2089PubMedGoogle Scholar
  198. 198.
    Luo J et al (2009) A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Cell 137(5):835–848PubMedCentralPubMedGoogle Scholar
  199. 199.
    Katayama H et al (2004) Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Nat Genet 36(1):55–62PubMedGoogle Scholar
  200. 200.
    Liu Q et al (2004) Aurora-A abrogation of p53 DNA binding and transactivation activity by phosphorylation of serine 215. J Biol Chem 279(50):52175–52182PubMedGoogle Scholar
  201. 201.
    Yoon MJ et al (2012) Aurora B confers cancer cell resistance to TRAIL-induced apoptosis via phosphorylation of survivin. Carcinogenesis 33(3):492–500PubMedGoogle Scholar
  202. 202.
    Quinn JE et al (2003) BRCA1 functions as a differential modulator of chemotherapy-induced apoptosis. Cancer Res 63(19):6221–6228PubMedGoogle Scholar
  203. 203.
    Weaver BA, Cleveland DW (2005) Decoding the links between mitosis, cancer, and chemotherapy: the mitotic checkpoint, adaptation, and cell death. Cancer Cell 8(1):7–12PubMedGoogle Scholar
  204. 204.
    Gascoigne KE, Taylor SS (2008) Cancer cells display profound intra- and interline variation following prolonged exposure to antimitotic drugs. Cancer Cell 14(2):111–122PubMedGoogle Scholar
  205. 205.
    Bekier ME, Fischbach R, Lee J, Taylor WR (2009) Length of mitotic arrest induced by microtubule-stabilizing drugs determines cell death after mitotic exit. Mol Cancer Ther 8(6):1646–1654PubMedGoogle Scholar
  206. 206.
    Goldspiel BR (1997) Clinical overview of the taxanes. Pharmacotherapy 17(5 Pt 2):110S–125SPubMedGoogle Scholar
  207. 207.
    Huang HC, Shi J, Orth JD, Mitchison TJ (2009) Evidence that mitotic exit is a better cancer therapeutic target than spindle assembly. Cancer Cell 16(4):347–358PubMedCentralPubMedGoogle Scholar
  208. 208.
    Bhat KM, Setaluri V (2007) Microtubule-associated proteins as targets in cancer chemotherapy. Clin Cancer Res 13(10):2849–2854PubMedGoogle Scholar
  209. 209.
    Kavallaris M et al (2001) Multiple microtubule alterations are associated with Vinca alkaloid resistance in human leukemia cells. Cancer Res 61(15):5803–5809PubMedGoogle Scholar
  210. 210.
    Alli E, Yang JM, Ford JM, Hait WN (2007) Reversal of stathmin-mediated resistance to paclitaxel and vinblastine in human breast carcinoma cells. Mol Pharmacol 71(5):1233–1240PubMedGoogle Scholar
  211. 211.
    Spankuch B et al (2006) Down-regulation of Polo-like kinase 1 elevates drug sensitivity of breast cancer cells in vitro and in vivo. Cancer Res 66(11):5836–5846PubMedGoogle Scholar
  212. 212.
    Spankuch B, Kurunci-Csacsko E, Kaufmann M, Strebhardt K (2007) Rational combinations of siRNAs targeting Plk1 with breast cancer drugs. Oncogene 26(39):5793–5807PubMedGoogle Scholar
  213. 213.
    Promkan M, Liu G, Patmasiriwat P, Chakrabarty S (2011) BRCA1 suppresses the expression of survivin and promotes sensitivity to paclitaxel through the calcium sensing receptor (CaSR) in human breast cancer cells. Cell Calcium 49(2):79–88PubMedGoogle Scholar
  214. 214.
    Chen L et al (2013) Survivin status affects prognosis and chemosensitivity in epithelial ovarian cancer. Int J Gynecol Cancer 23(2):256–263PubMedGoogle Scholar
  215. 215.
    Chello PL, Sirotnak FM (1981) Increased schedule-dependent synergism of vindesine versus vincristine in combination with methotrexate against L1210 leukemia. Cancer Treat Rep 65(11–12):1049–1053PubMedGoogle Scholar
  216. 216.
    Kano Y, Ohnuma T, Okano T, Holland JF (1988) Effects of vincristine in combination with methotrexate and other antitumor agents in human acute lymphoblastic leukemia cells in culture. Cancer Res 48(2):351–356PubMedGoogle Scholar
  217. 217.
    Cardoso F et al (2009) International guidelines for management of metastatic breast cancer: combination vs sequential single-agent chemotherapy. J Natl Cancer Inst 101(17):1174–1181PubMedCentralPubMedGoogle Scholar
  218. 218.
    Gobbi PG, Ferreri AJ, Ponzoni M, Levis A (2013) Hodgkin lymphoma. Crit Rev Oncol Hematol 85(2):216–237PubMedGoogle Scholar
  219. 219.
    Von Hoff DD et al (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369(18):1691–1703Google Scholar
  220. 220.
    Martin-Lluesma S, Stucke VM, Nigg EA (2002) Role of Hec1 in spindle checkpoint signaling and kinetochore recruitment of Mad1/Mad2. Science 297(5590):2267–2270PubMedGoogle Scholar
  221. 221.
    Wu G et al (2008) Small molecule targeting the Hec1/Nek2 mitotic pathway suppresses tumor cell growth in culture and in animal. Cancer Res 68(20):8393–8399PubMedCentralPubMedGoogle Scholar
  222. 222.
    Altieri DC (2003) Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene 22(53):8581–8589PubMedGoogle Scholar
  223. 223.
    Quintyne NJ, Reing JE, Hoffelder DR, Gollin SM, Saunders WS (2005) Spindle multipolarity is prevented by centrosomal clustering. Science 307(5706):127–129PubMedGoogle Scholar
  224. 224.
    Chang H et al (2012) The TPX2 gene is a promising diagnostic and therapeutic target for cervical cancer. Oncol Rep 27(5):1353–1359PubMedGoogle Scholar
  225. 225.
    Hsu PK et al (2014) TPX2 expression is associated with cell proliferation and patient outcome in esophageal squamous cell carcinoma. J Gastroenterol 49:1231–1240PubMedGoogle Scholar
  226. 226.
    Kanehira M et al (2007) Oncogenic role of MPHOSPH1, a cancer-testis antigen specific to human bladder cancer. Cancer Res 67(7):3276–3285PubMedGoogle Scholar
  227. 227.
    Shimo A et al (2007) Elevated expression of protein regulator of cytokinesis 1, involved in the growth of breast cancer cells. Cancer Sci 98(2):174–181PubMedGoogle Scholar
  228. 228.
    Ngan VK et al (2000) Novel actions of the antitumor drugs vinflunine and vinorelbine on microtubules. Cancer Res 60(18):5045–5051PubMedGoogle Scholar
  229. 229.
    Salmela AL, Kallio MJ (2013) Mitosis as an anti-cancer drug target. Chromosoma 122(5):431–449PubMedGoogle Scholar
  230. 230.
    Nakahara T et al (2011) Broad spectrum and potent antitumor activities of YM155, a novel small-molecule survivin suppressant, in a wide variety of human cancer cell lines and xenograft models. Cancer Sci 102(3):614–621PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  1. 1.Tumor Initiation and Maintenance ProgramSanford-Burnham Medical Research InstituteLa JollaUSA

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