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Bioprobes pp 11-35 | Cite as

Cell Proliferation and Differentiation

  • Nobumoto WatanabeEmail author
  • Hiroyuki Osada
Chapter
  • 460 Downloads

Abstract

Cell proliferation and differentiation are highly coordinated by cellular regulatory proteins. These proteins receive and transduce signals from external and internal stimuli and determine cell fate accordingly. When one or more of these strict control systems are impaired, cells begin to grow disorderly and become malignant. Even in normal development, these systems regulate the capacity for differentiation—i.e., pluripotency—and modulate cell differentiation. The artificial induction of factors that are essential for pluripotency has recently been shown to render differentiated cells undifferentiated.

In this chapter, several essential systems for cell proliferation and differentiation are described, as are recently identified small molecules that regulate them. Small molecules that inhibit the activity of factors that mediate malignant tumor cell growth can be exploited for cancer therapy. Small molecules also render cells undifferentiated. In addition, there are many small molecules that regulate the activity of cellular regulatory proteins and can be valuable tools to study the signaling systems in growth and differentiation—i.e., bioprobes.

Keywords

Cell growth Cell cycle Protein kinase Small molecule Signal transduction Protein phosphorylation 

References

  1. 1.
    Ullrich A, Schlessinger J (1990) Signal transduction by receptors with tyrosine kinase activity. Cell 61(2):203–212PubMedCrossRefGoogle Scholar
  2. 2.
    Schlessinger J (2002) Ligand-induced, receptor-mediated dimerization and activation of EGF receptor. Cell 110(6):669–672PubMedCrossRefGoogle Scholar
  3. 3.
    Roberts PJ, Der CJ (2007) Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 26(22):3291–3310. doi: 10.1038/sj.onc.1210422 PubMedCrossRefGoogle Scholar
  4. 4.
    Giancotti FG, Ruoslahti E (1999) Integrin signaling. Science 285(5430):1028–1032PubMedCrossRefGoogle Scholar
  5. 5.
    Schlaepfer DD, Mitra SK (2004) Multiple connections link FAK to cell motility and invasion. Curr Opin Genet Dev 14(1):92–101. doi: 10.1016/j.gde.2003.12.002 PubMedCrossRefGoogle Scholar
  6. 6.
    Rowley JD (1973) Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243(5405):290–293PubMedCrossRefGoogle Scholar
  7. 7.
    Groffen J, Stephenson JR, Heisterkamp N, de Klein A, Bartram CR, Grosveld G (1984) Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell 36(1):93–99PubMedCrossRefGoogle Scholar
  8. 8.
    Hazlehurst LA, Bewry NN, Nair RR, Pinilla-Ibarz J (2009) Signaling networks associated with BCR-ABL-dependent transformation. Cancer Control 16(2):100–107PubMedGoogle Scholar
  9. 9.
    De Braekeleer E, Douet-Guilbert N, Rowe D, Bown N, Morel F, Berthou C, Ferec C, De Braekeleer M (2011) ABL1 fusion genes in hematological malignancies: a review. Eur J Haematol 86(5):361–371. doi: 10.1111/j.1600-0609.2011.01586.x PubMedCrossRefGoogle Scholar
  10. 10.
    Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB (1996) Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 2(5):561–566PubMedCrossRefGoogle Scholar
  11. 11.
    Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H (2007) Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448(7153):561–566. doi: 10.1038/nature05945 PubMedCrossRefGoogle Scholar
  12. 12.
    Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Janne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, Iafrate AJ (2010) Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 363(18):1693–1703. doi: 10.1056/NEJMoa1006448 PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Choi YL, Soda M, Yamashita Y, Ueno T, Takashima J, Nakajima T, Yatabe Y, Takeuchi K, Hamada T, Haruta H, Ishikawa Y, Kimura H, Mitsudomi T, Tanio Y, Mano H, Group ALKLCS (2010) EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N Engl J Med 363(18):1734–1739. doi: 10.1056/NEJMoa1007478 PubMedCrossRefGoogle Scholar
  14. 14.
    Sasaki T, Okuda K, Zheng W, Butrynski J, Capelletti M, Wang L, Gray NS, Wilner K, Christensen JG, Demetri G, Shapiro GI, Rodig SJ, Eck MJ, Janne PA (2010) The neuroblastoma-associated F1174 L ALK mutation causes resistance to an ALK kinase inhibitor in ALK-translocated cancers. Cancer Res 70(24):10038–10043. doi: 10.1158/0008-5472.CAN-10-2956 PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Kohno T, Ichikawa H, Totoki Y, Yasuda K, Hiramoto M, Nammo T, Sakamoto H, Tsuta K, Furuta K, Shimada Y, Iwakawa R, Ogiwara H, Oike T, Enari M, Schetter AJ, Okayama H, Haugen A, Skaug V, Chiku S, Yamanaka I, Arai Y, Watanabe S, Sekine I, Ogawa S, Harris CC, Tsuda H, Yoshida T, Yokota J, Shibata T (2012) KIF5B-RET fusions in lung adenocarcinoma. Nat Med 18(3):375–377. doi: 10.1038/nm.2644 PubMedCrossRefGoogle Scholar
  16. 16.
    Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H, Nardone J, Lee K, Reeves C, Li Y, Hu Y, Tan Z, Stokes M, Sullivan L, Mitchell J, Wetzel R, Macneill J, Ren JM, Yuan J, Bakalarski CE, Villen J, Kornhauser JM, Smith B, Li D, Zhou X, Gygi SP, Gu TL, Polakiewicz RD, Rush J, Comb MJ (2007) Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131(6):1190–1203. doi: 10.1016/j.cell.2007.11.025 PubMedCrossRefGoogle Scholar
  17. 17.
    Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, Hatano S, Asaka R, Hamanaka W, Ninomiya H, Uehara H, Lim Choi Y, Satoh Y, Okumura S, Nakagawa K, Mano H, Ishikawa Y (2012) RET, ROS1 and ALK fusions in lung cancer. Nat Med 18(3):378–381. doi: 10.1038/nm.2658 PubMedCrossRefGoogle Scholar
  18. 18.
    Bible KC, Kaufmann SH (1996) Flavopiridol: a cytotoxic flavone that induces cell death in noncycling A549 human lung carcinoma cells. Cancer Res 56(21):4856–4861PubMedGoogle Scholar
  19. 19.
    Parker BW, Kaur G, Nieves-Neira W, Taimi M, Kohlhagen G, Shimizu T, Losiewicz MD, Pommier Y, Sausville EA, Senderowicz AM (1998) Early induction of apoptosis in hematopoietic cell lines after exposure to flavopiridol. Blood 91(2):458–465PubMedGoogle Scholar
  20. 20.
    Lam LT, Pickeral OK, Peng AC, Rosenwald A, Hurt EM, Giltnane JM, Averett LM, Zhao H, Davis RE, Sathyamoorthy M, Wahl LM, Harris ED, Mikovits JA, Monks AP, Hollingshead MG, Sausville EA, Staudt LM (2001) Genomic-scale measurement of mRNA turnover and the mechanisms of action of the anti-cancer drug flavopiridol. Genome Biol 2(10):RESEARCH0041PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Byrd JC, Peterson BL, Gabrilove J, Odenike OM, Grever MR, Rai K, Larson RA, Cancer, Leukemia Group B (2005) Treatment of relapsed chronic lymphocytic leukemia by 72-hour continuous infusion or 1-hour bolus infusion of flavopiridol: results from Cancer and Leukemia Group B study 19805. Clin Cancer Res 11(11):4176–4181. doi: 10.1158/1078-0432.CCR-04-2276 PubMedCrossRefGoogle Scholar
  22. 22.
    Jones JA, Kraut EH, Deam D, Byrd JC, Grever MR (2012) Hematologic improvement after flavopiridol treatment of pentostatin and rituximab refractory hairy cell leukemia. Leuk Lymphoma 53(3):490–491. doi: 10.3109/10428194.2011.600484 PubMedCrossRefGoogle Scholar
  23. 23.
    McClue SJ, Blake D, Clarke R, Cowan A, Cummings L, Fischer PM, MacKenzie M, Melville J, Stewart K, Wang S, Zhelev N, Zheleva D, Lane DP (2002) In vitro and in vivo antitumor properties of the cyclin dependent kinase inhibitor CYC202 (R-roscovitine). Int J Cancer 102(5):463–468. doi: 10.1002/ijc.10738 PubMedCrossRefGoogle Scholar
  24. 24.
    Lacrima K, Rinaldi A, Vignati S, Martin V, Tibiletti MG, Gaidano G, Catapano CV, Bertoni F (2007) Cyclin-dependent kinase inhibitor seliciclib shows in vitro activity in diffuse large B-cell lymphomas. Leuk Lymphoma 48(1):158–167. doi: 10.1080/10428190601026562 PubMedCrossRefGoogle Scholar
  25. 25.
    Parry D, Guzi T, Shanahan F, Davis N, Prabhavalkar D, Wiswell D, Seghezzi W, Paruch K, Dwyer MP, Doll R, Nomeir A, Windsor W, Fischmann T, Wang Y, Oft M, Chen T, Kirschmeier P, Lees EM (2010) Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor. Mol Cancer Ther 9(8):2344–2353. doi: 10.1158/1535-7163.MCT-10-0324 PubMedCrossRefGoogle Scholar
  26. 26.
    Stephenson JJ, Nemunaitis J, Joy AA, Martin JC, Jou YM, Zhang D, Statkevich P, Yao SL, Zhu Y, Zhou H, Small K, Bannerji R, Edelman MJ (2014) Randomized phase 2 study of the cyclin-dependent kinase inhibitor dinaciclib (MK-7965) versus erlotinib in patients with non-small cell lung cancer. Lung Cancer 83(2):219–223. doi: 10.1016/j.lungcan.2013.11.020 PubMedCrossRefGoogle Scholar
  27. 27.
    Fry DW, Harvey PJ, Keller PR, Elliott WL, Meade M, Trachet E, Albassam M, Zheng X, Leopold WR, Pryer NK, Toogood PL (2004) Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther 3(11):1427–1438PubMedGoogle Scholar
  28. 28.
    Rocca A, Farolfi A, Bravaccini S, Schirone A, Amadori D (2014) Palbociclib (PD 0332991): targeting the cell cycle machinery in breast cancer. Expert Opin Pharmacother 15(3):407–420. doi: 10.1517/14656566.2014.870555 PubMedCrossRefGoogle Scholar
  29. 29.
    Lens SM, Voest EE, Medema RH (2010) Shared and separate functions of polo-like kinases and aurora kinases in cancer. Nat Rev Cancer 10(12):825–841. doi: 10.1038/nrc2964 PubMedCrossRefGoogle Scholar
  30. 30.
    Barr FA, Sillje HH, Nigg EA (2004) Polo-like kinases and the orchestration of cell division. Nat Rev Mol Cell Biol 5(6):429–440. doi: 10.1038/nrm1401 PubMedCrossRefGoogle Scholar
  31. 31.
    van Vugt MA, Medema RH (2005) Getting in and out of mitosis with polo-like kinase-1. Oncogene 24(17):2844–2859. doi: 10.1038/sj.onc.1208617 PubMedCrossRefGoogle Scholar
  32. 32.
    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):1701–1713PubMedCrossRefGoogle Scholar
  33. 33.
    Sumara I, Gimenez-Abian JF, Gerlich D, Hirota T, Kraft C, de la Torre C, Ellenberg J, Peters JM (2004) Roles of polo-like kinase 1 in the assembly of functional mitotic spindles. Curr Biol 14(19):1712–1722. doi: 10.1016/j.cub.2004.09.049 PubMedCrossRefGoogle Scholar
  34. 34.
    van Vugt MA, van de Weerdt BC, Vader G, Janssen H, Calafat J, Klompmaker R, Wolthuis RM, Medema RH (2004) Polo-like kinase-1 is required for bipolar spindle formation but is dispensable for anaphase promoting complex/Cdc20 activation and initiation of cytokinesis. J Biol Chem 279(35):36841–36854. doi: 10.1074/jbc.M313681200 PubMedCrossRefGoogle Scholar
  35. 35.
    Kumagai A, Dunphy WG (1996) Purification and molecular cloning of Plx1, a Cdc25-regulatory kinase from Xenopus egg extracts. Science 273(5280):1377–1380PubMedCrossRefGoogle Scholar
  36. 36.
    Toyoshima-Morimoto F, Taniguchi E, Nishida E (2002) Plk1 promotes nuclear translocation of human Cdc25C during prophase. EMBO Rep 3(4):341–348. doi: 10.1093/embo-reports/kvf069 PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Watanabe N, Arai H, Iwasaki J, Shiina M, Ogata K, Hunter T, Osada H (2005) Cyclin-dependent kinase (CDK) phosphorylation destabilizes somatic Wee1 via multiple pathways. Proc Natl Acad Sci U S A 102(33):11663–11668. doi: 10.1073/pnas.0500410102 PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Watanabe N, Arai H, Nishihara Y, Taniguchi M, Watanabe N, Hunter T, Osada H (2004) M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP. Proc Natl Acad Sci U S A 101(13):4419–4424. doi: 10.1073/pnas.0307700101 PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Elowe S, Hummer S, Uldschmid A, Li X, Nigg EA (2007) Tension-sensitive Plk1 phosphorylation on BubR1 regulates the stability of kinetochore microtubule interactions. Genes Dev 21(17):2205–2219. doi: 10.1101/gad.436007 PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Ahonen LJ, Kallio MJ, Daum JR, Bolton M, Manke IA, Yaffe MB, Stukenberg PT, Gorbsky GJ (2005) Polo-like kinase 1 creates the tension-sensing 3F3/2 phosphoepitope and modulates the association of spindle-checkpoint proteins at kinetochores. Curr Biol 15(12):1078–1089. doi: 10.1016/j.cub.2005.05.026 PubMedCrossRefGoogle Scholar
  41. 41.
    Wong OK, Fang G (2005) Plx1 is the 3F3/2 kinase responsible for targeting spindle checkpoint proteins to kinetochores. J Cell Biol 170(5):709–719. doi: 10.1083/jcb.200502163 PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Wong OK, Fang G (2007) Cdk1 phosphorylation of BubR1 controls spindle checkpoint arrest and Plk1-mediated formation of the 3F3/2 epitope. J Cell Biol 179(4):611–617. doi: 10.1083/jcb.200708044 PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Nishino M, Kurasawa Y, Evans R, Lin SH, Brinkley BR, Yu-Lee LY (2006) NudC is required for Plk1 targeting to the kinetochore and chromosome congression. Curr Biol 16(14):1414–1421. doi: 10.1016/j.cub.2006.05.052 PubMedCrossRefGoogle Scholar
  44. 44.
    Losada A, Hirano M, Hirano T (2002) Cohesin release is required for sister chromatid resolution, but not for condensin-mediated compaction, at the onset of mitosis. Genes Dev 16(23):3004–3016. doi: 10.1101/gad.249202 PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Sumara I, Vorlaufer E, Stukenberg PT, Kelm O, Redemann N, Nigg EA, Peters JM (2002) The dissociation of cohesin from chromosomes in prophase is regulated by polo-like kinase. Mol Cell 9(3):515–525PubMedCrossRefGoogle Scholar
  46. 46.
    Howard S, Berdini V, Boulstridge JA, Carr MG, Cross DM, Curry J, Devine LA, Early TR, Fazal L, Gill AL, Heathcote M, Maman S, Matthews JE, McMenamin RL, Navarro EF, O’Brien MA, O’Reilly M, Rees DC, Reule M, Tisi D, Williams G, Vinkovic M, Wyatt PG (2009) Fragment-based discovery of the pyrazol-4-yl urea (AT9283), a multitargeted kinase inhibitor with potent aurora kinase activity. J Med Chem 52(2):379–388. doi: 10.1021/jm800984v PubMedCrossRefGoogle Scholar
  47. 47.
    Qi W, Tang Z, Yu H (2006) Phosphorylation- and polo-box-dependent binding of Plk1 to Bub1 is required for the kinetochore localization of Plk1. Mol Biol Cell 17(8):3705–3716. doi: 10.1091/mbc.E06-03-0240 PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Lee KS, Yuan YL, Kuriyama R, Erikson RL (1995) Plk is an M-phase-specific protein kinase and interacts with a kinesin-like protein, CHO1/MKLP-1. Mol Cell Biol 15(12):7143–7151PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Neef R, Preisinger C, Sutcliffe J, Kopajtich R, Nigg EA, Mayer TU, Barr FA (2003) Phosphorylation of mitotic kinesin-like protein 2 by polo-like kinase 1 is required for cytokinesis. J Cell Biol 162(5):863–875. doi: 10.1083/jcb.200306009 PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Zhou T, Aumais JP, Liu X, Yu-Lee LY, Erikson RL (2003) A role for Plk1 phosphorylation of NudC in cytokinesis. Dev Cell 5(1):127–138PubMedCrossRefGoogle Scholar
  51. 51.
    Hudson JW, Kozarova A, Cheung P, Macmillan JC, Swallow CJ, Cross JC, Dennis JW (2001) Late mitotic failure in mice lacking Sak, a polo-like kinase. Curr Biol 11(6):441–446PubMedCrossRefGoogle Scholar
  52. 52.
    Seong YS, Kamijo K, Lee JS, Fernandez E, Kuriyama R, Miki T, Lee KS (2002) A spindle checkpoint arrest and a cytokinesis failure by the dominant-negative polo-box domain of Plk1 in U-2 OS cells. J Biol Chem 277(35):32282–32293. doi: 10.1074/jbc.M202602200 PubMedCrossRefGoogle Scholar
  53. 53.
    Elia AE, Cantley LC, Yaffe MB (2003) Proteomic screen finds pSer/pThr-binding domain localizing Plk1 to mitotic substrates. Science 299(5610):1228–1231. doi: 10.1126/science.1079079 PubMedCrossRefGoogle Scholar
  54. 54.
    Elia AE, Rellos P, Haire LF, Chao JW, Ivins FJ, Hoepker K, Mohammad D, Cantley LC, Smerdon SJ, Yaffe MB (2003) The molecular basis for phosphodependent substrate targeting and regulation of Plks by the polo-box domain. Cell 115(1):83–95PubMedCrossRefGoogle Scholar
  55. 55.
    Liao JJ (2007) Molecular recognition of protein kinase binding pockets for design of potent and selective kinase inhibitors. J Med Chem 50(3):409–424. doi: 10.1021/jm0608107 PubMedCrossRefGoogle Scholar
  56. 56.
    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):6459–6466. doi: 10.1158/1078-0432.CCR-11-0541 PubMedCrossRefGoogle Scholar
  57. 57.
    Gumireddy K, Reddy MV, Cosenza SC, Boominathan R, Baker SJ, Papathi N, Jiang J, Holland J, Reddy EP (2005) ON01910, a non-ATP-competitive small molecule inhibitor of Plk1, is a potent anticancer agent. Cancer Cell 7(3):275–286. doi: 10.1016/j.ccr.2005.02.009 PubMedCrossRefGoogle Scholar
  58. 58.
    Kothe M, Kohls D, Low S, Coli R, Rennie GR, Feru F, Kuhn C, Ding YH (2007) Selectivity-determining residues in Plk1. Chem Biol Drug Des 70(6):540–546. doi: 10.1111/j.1747-0285.2007.00594.x PubMedCrossRefGoogle Scholar
  59. 59.
    Steegmaier M, Hoffmann M, Baum A, Lenart P, Petronczki M, Krssak M, Gurtler U, Garin-Chesa P, Lieb S, Quant J, Grauert M, Adolf GR, Kraut N, Peters JM, Rettig WJ (2007) BI 2536, a potent and selective inhibitor of polo-like kinase 1, inhibits tumor growth in vivo. Curr Biol 17(4):316–322. doi: 10.1016/j.cub.2006.12.037 PubMedCrossRefGoogle Scholar
  60. 60.
    Lenart P, Petronczki M, Steegmaier M, Di Fiore B, Lipp JJ, Hoffmann M, Rettig WJ, Kraut N, Peters JM (2007) The small-molecule inhibitor BI 2536 reveals novel insights into mitotic roles of polo-like kinase 1. Curr Biol 17(4):304–315. doi: 10.1016/j.cub.2006.12.046 PubMedCrossRefGoogle Scholar
  61. 61.
    Jimeno A, Li J, Messersmith WA, Laheru D, Rudek MA, Maniar M, Hidalgo M, Baker SD, Donehower RC (2008) Phase I study of ON 01910.Na, a novel modulator of the polo-like kinase 1 pathway, in adult patients with solid tumors. J Clin Oncol 26(34):5504–5510. doi: 10.1200/JCO.2008.17.9788 PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Mross K, Frost A, Steinbild S, Hedbom S, Rentschler J, Kaiser R, Rouyrre N, Trommeshauser D, Hoesl CE, Munzert G (2008) Phase I dose escalation and pharmacokinetic study of BI 2536, a novel polo-like kinase 1 inhibitor, in patients with advanced solid tumors. J Clin Oncol 26(34):5511–5517. doi: 10.1200/JCO.2008.16.1547 PubMedCrossRefGoogle Scholar
  63. 63.
    Hofheinz RD, Al-Batran SE, Hochhaus A, Jager E, Reichardt VL, Fritsch H, Trommeshauser D, Munzert G (2010) An open-label, phase I study of the polo-like kinase-1 inhibitor, BI 2536, in patients with advanced solid tumors. Clin Cancer Res 16(18):4666–4674. doi: 10.1158/1078-0432.CCR-10-0318 PubMedCrossRefGoogle Scholar
  64. 64.
    Sebastian M, Reck M, Waller CF, Kortsik C, Frickhofen N, Schuler M, Fritsch H, Gaschler-Markefski B, Hanft G, Munzert G, von Pawel J (2010) The efficacy and safety of BI 2536, a novel Plk-1 inhibitor, in patients with stage IIIB/IV non-small cell lung cancer who had relapsed after, or failed, chemotherapy: results from an open-label, randomized phase II clinical trial. J Thorac Oncol 5(7):1060–1067. doi: 10.1097/JTO.0b013e3181d95dd4 PubMedCrossRefGoogle Scholar
  65. 65.
    Gilmartin AG, Bleam MR, Richter MC, Erskine SG, Kruger RG, Madden L, Hassler DF, Smith GK, Gontarek RR, Courtney MP, Sutton D, Diamond MA, Jackson JR, Laquerre SG (2009) Distinct concentration-dependent effects of the polo-like kinase 1–specific inhibitor GSK461364A, including differential effect on apoptosis. Cancer Res 69(17):6969–6977. doi: 10.1158/0008-5472.CAN-09-0945 PubMedCrossRefGoogle Scholar
  66. 66.
    Olmos D, Barker D, Sharma R, Brunetto AT, Yap TA, Taegtmeyer AB, Barriuso J, Medani H, Degenhardt YY, Allred AJ, Smith DA, Murray SC, Lampkin TA, Dar MM, Wilson R, de Bono JS, Blagden SP (2011) Phase I study of GSK461364, a specific and competitive polo-like kinase 1 inhibitor, in patients with advanced solid malignancies. Clin Cancer Res 17(10):3420–3430. doi: 10.1158/1078-0432.CCR-10-2946 PubMedCrossRefGoogle Scholar
  67. 67.
    Rudolph D, Steegmaier M, Hoffmann M, Grauert M, Baum A, Quant J, Haslinger C, Garin-Chesa P, Adolf GR (2009) BI 6727, a polo-like kinase inhibitor with improved pharmacokinetic profile and broad antitumor activity. Clin Cancer Res 15(9):3094–3102. doi: 10.1158/1078-0432.CCR-08-2445 PubMedCrossRefGoogle Scholar
  68. 68.
    Watanabe N, Sekine T, Takagi M, Iwasaki J, Imamoto N, Kawasaki H, Osada H (2009) Deficiency in chromosome congression by the inhibition of Plk1 polo box domain–dependent recognition. J Biol Chem 284(4):2344–2353. doi: 10.1074/jbc.M805308200 PubMedCrossRefGoogle Scholar
  69. 69.
    Murugan RN, Park JE, Kim EH, Shin SY, Cheong C, Lee KS, Bang JK (2011) Plk1-targeted small molecule inhibitors: molecular basis for their potency and specificity. Mol Cells 32(3):209–220. doi: 10.1007/s10059-011-0126-3 PubMedCrossRefGoogle Scholar
  70. 70.
    Reindl W, Yuan J, Kramer A, Strebhardt K, Berg T (2008) Inhibition of polo-like kinase 1 by blocking polo-box domain–dependent protein-protein interactions. Chem Biol 15(5):459–466. doi: 10.1016/j.chembiol.2008.03.013 PubMedCrossRefGoogle Scholar
  71. 71.
    Liao C, Park JE, Bang JK, Nicklaus MC, Lee KS (2010) Exploring potential binding modes of small drug-like molecules to the polo-box domain of human polo-like kinase 1. ACS Med Chem Lett 1(3):110–114. doi: 10.1021/ml100020e PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Watanabe N, Osada H (2012) Phosphorylation-dependent protein-protein interaction modules as potential molecular targets for cancer therapy. Curr Drug Targets 13(13):1654–1658PubMedCrossRefGoogle Scholar
  73. 73.
    Glover DM, Leibowitz MH, McLean DA, Parry H (1995) Mutations in Aurora prevent centrosome separation leading to the formation of monopolar spindles. Cell 81(1):95–105PubMedCrossRefGoogle Scholar
  74. 74.
    Carmena M, Earnshaw WC (2003) The cellular geography of aurora kinases. Nat Rev Mol Cell Biol 4(11):842–854. doi: 10.1038/nrm1245 PubMedCrossRefGoogle Scholar
  75. 75.
    Chen HL, Tang CJ, Chen CY, Tang TK (2005) Overexpression of an Aurora-C kinase-deficient mutant disrupts the Aurora-B/INCENP complex and induces polyploidy. J Biomed Sci 12(2):297–310. doi: 10.1007/s11373-005-0980-0 PubMedCrossRefGoogle Scholar
  76. 76.
    Adams RR, Maiato H, Earnshaw WC, Carmena M (2001) Essential roles of Drosophila inner centromere protein (INCENP) and Aurora B in histone H3 phosphorylation, metaphase chromosome alignment, kinetochore disjunction, and chromosome segregation. J Cell Biol 153(4):865–880PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Goto H, Yasui Y, Nigg EA, Inagaki M (2002) Aurora-B phosphorylates histone H3 at serine28 with regard to the mitotic chromosome condensation. Genes Cells 7(1):11–17PubMedCrossRefGoogle Scholar
  78. 78.
    Yan X, Cao L, Li Q, Wu Y, Zhang H, Saiyin H, Liu X, Zhang X, Shi Q, Yu L (2005) Aurora C is directly associated with Survivin and required for cytokinesis. Genes Cells 10(6):617–626. doi: 10.1111/j.1365-2443.2005.00863.x PubMedCrossRefGoogle Scholar
  79. 79.
    Hauf S, Cole RW, LaTerra S, Zimmer C, Schnapp G, Walter R, Heckel A, van Meel J, Rieder CL, Peters JM (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):281–294. doi: 10.1083/jcb.200208092 PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Ditchfield C, Johnson VL, Tighe A, Ellston R, Haworth C, Johnson T, Mortlock A, Keen N, Taylor SS (2003) Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. J Cell Biol 161(2):267–280. doi: 10.1083/jcb.200208091 PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Bebbington D, Binch H, Charrier JD, Everitt S, Fraysse D, Golec J, Kay D, Knegtel R, Mak C, Mazzei F, Miller A, Mortimore M, O’Donnell M, Patel S, Pierard F, Pinder J, Pollard J, Ramaya S, Robinson D, Rutherford A, Studley J, Westcott J (2009) The discovery of the potent aurora inhibitor MK-0457 (VX-680). Bioorg Med Chem Lett 19(13):3586–3592. doi: 10.1016/j.bmcl.2009.04.136 PubMedCrossRefGoogle Scholar
  82. 82.
    Harrington EA, Bebbington D, Moore J, Rasmussen RK, Ajose-Adeogun AO, Nakayama T, Graham JA, Demur C, Hercend T, Diu-Hercend A, Su M, Golec JM, Miller KM (2004) VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat Med 10(3):262–267. doi: 10.1038/nm1003 PubMedCrossRefGoogle Scholar
  83. 83.
    Cheetham GM, Charlton PA, Golec JM, Pollard JR (2007) Structural basis for potent inhibition of the Aurora kinases and a T315I multi-drug resistant mutant form of Abl kinase by VX-680. Cancer Lett 251(2):323–329. doi: 10.1016/j.canlet.2006.12.004 PubMedCrossRefGoogle Scholar
  84. 84.
    Fancelli D, Berta D, Bindi S, Cameron A, Cappella P, Carpinelli P, Catana C, Forte B, Giordano P, Giorgini ML, Mantegani S, Marsiglio A, Meroni M, Moll J, Pittala V, Roletto F, Severino D, Soncini C, Storici P, Tonani R, Varasi M, Vulpetti A, Vianello P (2005) Potent and selective Aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition. J Med Chem 48(8):3080–3084. doi: 10.1021/jm049076m PubMedCrossRefGoogle Scholar
  85. 85.
    Arbitrario JP, Belmont BJ, Evanchik MJ, Flanagan WM, Fucini RV, Hansen SK, Harris SO, Hashash A, Hoch U, Hogan JN, Howlett AR, Jacobs JW, Lam JW, Ritchie SC, Romanowski MJ, Silverman JA, Stockett DE, Teague JN, Zimmerman KM, Taverna P (2010) SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol 65(4):707–717. doi: 10.1007/s00280-009-1076-8 PubMedCrossRefGoogle Scholar
  86. 86.
    McLaughlin J, Markovtsov V, Li H, Wong S, Gelman M, Zhu Y, Franci C, Lang D, Pali E, Lasaga J, Low C, Zhao F, Chang B, Gururaja TL, Xu W, Baluom M, Sweeny D, Carroll D, Sran A, Thota S, Parmer M, Romane A, Clemens G, Grossbard E, Qu K, Jenkins Y, Kinoshita T, Taylor V, Holland SJ, Argade A, Singh R, Pine P, Payan DG, Hitoshi Y (2010) Preclinical characterization of Aurora kinase inhibitor R763/AS703569 identified through an image-based phenotypic screen. J Cancer Res Clin Oncol 136(1):99–113. doi: 10.1007/s00432-009-0641-1 PubMedCrossRefGoogle Scholar
  87. 87.
    Hardwicke MA, Oleykowski CA, Plant R, Wang J, Liao Q, Moss K, Newlander K, Adams JL, Dhanak D, Yang J, Lai Z, Sutton D, Patrick D (2009) GSK1070916, a potent Aurora B/C kinase inhibitor with broad antitumor activity in tissue culture cells and human tumor xenograft models. Mol Cancer Ther 8(7):1808–1817. doi: 10.1158/1535-7163.MCT-09-0041 PubMedCrossRefGoogle Scholar
  88. 88.
    Curry J, Angove H, Fazal L, Lyons J, Reule M, Thompson N, Wallis N (2009) Aurora B kinase inhibition in mitosis: strategies for optimising the use of aurora kinase inhibitors such as AT9283. Cell Cycle 8(12):1921–1929PubMedCrossRefGoogle Scholar
  89. 89.
    Wang S, Midgley CA, Scaerou F, Grabarek JB, Griffiths G, Jackson W, Kontopidis G, McClue SJ, McInnes C, Meades C, Mezna M, Plater A, Stuart I, Thomas MP, Wood G, Clarke RG, Blake DG, Zheleva DI, Lane DP, Jackson RC, Glover DM, Fischer PM (2010) Discovery of N-phenyl-4-(thiazol-5-yl)pyrimidin-2-amine aurora kinase inhibitors. J Med Chem 53(11):4367–4378. doi: 10.1021/jm901913s PubMedCrossRefGoogle Scholar
  90. 90.
    Gorgun G, Calabrese E, Hideshima T, Ecsedy J, Perrone G, Mani M, Ikeda H, Bianchi G, Hu Y, Cirstea D, Santo L, Tai YT, Nahar S, Zheng M, Bandi M, Carrasco RD, Raje N, Munshi N, Richardson P, Anderson KC (2010) A novel Aurora-A kinase inhibitor MLN8237 induces cytotoxicity and cell-cycle arrest in multiple myeloma. Blood 115(25):5202–5213. doi: 10.1182/blood-2009-12-259523 PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Shimomura T, Hasako S, Nakatsuru Y, Mita T, Ichikawa K, Kodera T, Sakai T, Nambu T, Miyamoto M, Takahashi I, Miki S, Kawanishi N, Ohkubo M, Kotani H, Iwasawa Y (2010) MK-5108, a highly selective Aurora-A kinase inhibitor, shows antitumor activity alone and in combination with docetaxel. Mol Cancer Ther 9(1):157–166. doi: 10.1158/1535-7163.MCT-09-0609 PubMedCrossRefGoogle Scholar
  92. 92.
    Amin M, Minton SE, LoRusso PM, Krishnamurthi SS, Pickett CA, Lunceford J, Hille D, Mauro D, Stein MN, Wang-Gillam A, Trull L, Lockhart AC (2016) A phase I study of MK-5108, an oral aurora a kinase inhibitor, administered both as monotherapy and in combination with docetaxel, in patients with advanced or refractory solid tumors. Investig New Drugs 34(1):84–95. doi: 10.1007/s10637-015-0306-7 CrossRefGoogle Scholar
  93. 93.
    Fletcher GC, Brokx RD, Denny TA, Hembrough TA, Plum SM, Fogler WE, Sidor CF, Bray MR (2011) ENMD-2076 is an orally active kinase inhibitor with antiangiogenic and antiproliferative mechanisms of action. Mol Cancer Ther 10(1):126–137. doi: 10.1158/1535-7163.MCT-10-0574 PubMedCrossRefGoogle Scholar
  94. 94.
    Mortlock AA, Foote KM, Heron NM, Jung FH, Pasquet G, Lohmann JJ, Warin N, Renaud F, De Savi C, Roberts NJ, Johnson T, Dousson CB, Hill GB, Perkins D, Hatter G, Wilkinson RW, Wedge SR, Heaton SP, Odedra R, Keen NJ, Crafter C, Brown E, Thompson K, Brightwell S, Khatri L, Brady MC, Kearney S, McKillop D, Rhead S, Parry T, Green S (2007) Discovery, synthesis, and in vivo activity of a new class of pyrazoloquinazolines as selective inhibitors of aurora B kinase. J Med Chem 50(9):2213–2224. doi: 10.1021/jm061335f PubMedCrossRefGoogle Scholar
  95. 95.
    Collins GP, Eyre TA, Linton KM, Radford J, Vallance GD, Soilleux E, Hatton C (2015) A phase II trial of AZD1152 in relapsed/refractory diffuse large B-cell lymphoma. Br J Haematol 170(6):886–890. doi: 10.1111/bjh.13333 PubMedCrossRefGoogle Scholar
  96. 96.
    Wilkinson RW, Odedra R, Heaton SP, Wedge SR, Keen NJ, Crafter C, Foster JR, Brady MC, Bigley A, Brown E, Byth KF, Barrass NC, Mundt KE, Foote KM, Heron NM, Jung FH, Mortlock AA, Boyle FT, Green S (2007) AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosis. Clin Cancer Res 13(12):3682–3688. doi: 10.1158/1078-0432.CCR-06-2979 PubMedCrossRefGoogle Scholar
  97. 97.
    Yang J, Ikezoe T, Nishioka C, Tasaka T, Taniguchi A, Kuwayama Y, Komatsu N, Bandobashi K, Togitani K, Koeffler HP, Taguchi H, Yokoyama A (2007) AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivo. Blood 110(6):2034–2040. doi: 10.1182/blood-2007-02-073700 PubMedCrossRefGoogle Scholar
  98. 98.
    Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676. doi: 10.1016/j.cell.2006.07.024 PubMedCrossRefGoogle Scholar
  99. 99.
    Hou P, Li Y, Zhang X, Liu C, Guan J, Li H, Zhao T, Ye J, Yang W, Liu K, Ge J, Xu J, Zhang Q, Zhao Y, Deng H (2013) Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science 341(6146):651–654. doi: 10.1126/science.1239278 PubMedCrossRefGoogle Scholar
  100. 100.
    Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292(5819):154–156PubMedCrossRefGoogle Scholar
  101. 101.
    Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A 78(12):7634–7638PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH (1997) Viable offspring derived from fetal and adult mammalian cells. Nature 385(6619):810–813. doi: 10.1038/385810a0 PubMedCrossRefGoogle Scholar
  103. 103.
    Cowan CA, Atienza J, Melton DA, Eggan K (2005) Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science 309(5739):1369–1373. doi: 10.1126/science.1116447 PubMedCrossRefGoogle Scholar
  104. 104.
    Tada M, Takahama Y, Abe K, Nakatsuji N, Tada T (2001) Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Curr Biol 11(19):1553–1558PubMedCrossRefGoogle Scholar
  105. 105.
    Li Y, Zhang Q, Yin X, Yang W, Du Y, Hou P, Ge J, Liu C, Zhang W, Zhang X, Wu Y, Li H, Liu K, Wu C, Song Z, Zhao Y, Shi Y, Deng H (2011) Generation of iPSCs from mouse fibroblasts with a single gene, Oct4, and small molecules. Cell Res 21(1):196–204. doi: 10.1038/cr.2010.142 PubMedCrossRefGoogle Scholar
  106. 106.
    Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367(6464):645–648. doi: 10.1038/367645a0 PubMedCrossRefGoogle Scholar
  107. 107.
    Gottesman MM, Fojo T, Bates SE (2002) Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2(1):48–58. doi: 10.1038/nrc706 PubMedCrossRefGoogle Scholar
  108. 108.
    Ho MM, Ng AV, Lam S, Hung JY (2007) Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res 67(10):4827–4833. doi: 10.1158/0008-5472.CAN-06-3557 PubMedCrossRefGoogle Scholar
  109. 109.
    Zhang M, Mathur A, Zhang Y, Xi S, Atay S, Hong JA, Datrice N, Upham T, Kemp CD, Ripley RT, Wiegand G, Avital I, Fetsch P, Mani H, Zlott D, Robey R, Bates SE, Li X, Rao M, Schrump DS (2012) Mithramycin represses basal and cigarette smoke–induced expression of ABCG2 and inhibits stem cell signaling in lung and esophageal cancer cells. Cancer Res 72(16):4178–4192. doi: 10.1158/0008-5472.CAN-11-3983 PubMedCrossRefGoogle Scholar
  110. 110.
    Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, Lander ES (2009) Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 138(4):645–659. doi: 10.1016/j.cell.2009.06.034 PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Campos B, Wan F, Farhadi M, Ernst A, Zeppernick F, Tagscherer KE, Ahmadi R, Lohr J, Dictus C, Gdynia G, Combs SE, Goidts V, Helmke BM, Eckstein V, Roth W, Beckhove P, Lichter P, Unterberg A, Radlwimmer B, Herold-Mende C (2010) Differentiation therapy exerts antitumor effects on stem-like glioma cells. Clin Cancer Res 16(10):2715–2728. doi: 10.1158/1078-0432.CCR-09-1800 PubMedCrossRefGoogle Scholar
  112. 112.
    Sotiropoulou PA, Christodoulou MS, Silvani A, Herold-Mende C, Passarella D (2014) Chemical approaches to targeting drug resistance in cancer stem cells. Drug Discov Today. doi: 10.1016/j.drudis.2014.05.002 PubMedGoogle Scholar

Copyright information

© Springer Japan KK 2017

Authors and Affiliations

  1. 1.Bio-Active Compounds Discovery Research UnitRIKEN Center for Sustainable Resource ScienceWakoJapan
  2. 2.Chemical Biology Research GroupRIKEN Center for Sustainable Resource ScienceWakoJapan

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