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Regulation of paclitaxel activity by microtubule-associated proteins in cancer chemotherapy

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Abstract

Microtubules, highly dynamic components of the cytoskeleton, participate in diverse cellular activities such as mitosis, cell migration, and intracellular trafficking. Dysregulation of microtubule dynamics contributes to the development of serious diseases, including cancer. The dynamic properties and functions of microtubule network are regulated by microtubule-associated proteins. Paclitaxel, an anti-microtubule agent of the taxane family, has shown a success in clinical treatment of many cancer patients. However, the variable response activity of patients and acquired resistance to paclitaxel limit the clinical use of the drug. Accumulating studies show that microtubule-associated proteins can regulate paclitaxel sensitivity in a wide range of cancer types. In this review, we will describe the roles of various microtubule-associated proteins in the regulation of paclitaxel in cancers. Particularly, we will focus on the modulation of centrosomal proteins in paclitaxel resistance. Improved understandings of how these proteins act might predict treatment responses and provide insights into more rational chemotherapeutic regimens in clinical practice.

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Abbreviations

MAPs:

Microtubule-associated proteins

EB:

End-binding family protein

CLIP-170:

Cytoplasmic linker protein 170

Nlp:

Ninein-like protein

TACC:

Transforming acidic coiled coil

Rb:

Retinoblastoma protein

ERK1/2:

Extracellular signal-regulated kinase 1/2

SIK2:

Salt Inducible Kinase 2

Cep70:

Centrosomal protein 70

SAC:

Spindle assembly checkpoint

APC/C:

Anaphase promoting complex/cyclosome

KIF:

Kinesin superfamily protein

BLBC:

Basal-like breast cancer

References

  1. Desai A, Mitchison TJ (1997) Microtubule polymerization dynamics. Annu Rev Cell Dev Biol 13:83–117. doi:10.1146/annurev.cellbio.13.1.83

    Article  CAS  PubMed  Google Scholar 

  2. McIntosh JR, Grishchuk EL, West RR (2002) Chromosome-microtubule interactions during mitosis. Annu Rev Cell Dev Biol 18:193–219. doi:10.1146/annurev.cellbio.18.032002.132412

    Article  CAS  PubMed  Google Scholar 

  3. Doxsey S, Zimmerman W, Mikule K (2005) Centrosome control of the cell cycle. Trends Cell Biol 15(6):303–311. doi:10.1016/j.tcb.2005.04.008

    Article  CAS  PubMed  Google Scholar 

  4. Kirschner MW, Mitchison T (1986) Microtubule dynamics. Nature 324(6098):621. doi:10.1038/324621a0

    Article  CAS  PubMed  Google Scholar 

  5. Bhat KM, Setaluri V (2007) Microtubule-associated proteins as targets in cancer chemotherapy. Clin Cancer Res 13(10):2849–2854. doi:10.1158/1078-0432.CCR-06-3040

    Article  CAS  PubMed  Google Scholar 

  6. Liu M, Wang X, Yang Y, Li D, Ren H, Zhu Q, Chen Q, Han S, Hao J, Zhou J (2010) Ectopic expression of the microtubule-dependent motor protein Eg5 promotes pancreatic tumourigenesis. J Pathol 221(2):221–228. doi:10.1002/path.2706

    Article  CAS  PubMed  Google Scholar 

  7. Tala Xie S, Sun X, Sun X, Ran J, Zhang L, Li D, Liu M, Bao G, Zhou J (2014) Microtubule-associated protein Mdp3 promotes breast cancer growth and metastasis. Theranostics 4(10):1052–1061. doi:10.7150/thno.9727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Shi X, Li D, Wang Y, Liu S, Qin J, Wang J, Ran J, Zhang Y, Huang Q, Liu X, Zhou J, Liu M (2017) Discovery of centrosomal protein 70 as an important player in the development and progression of breast cancer. Am J Pathol 187(3):679–688. doi:10.1016/j.ajpath.2016.11.005

    Article  CAS  PubMed  Google Scholar 

  9. Barok M, Joensuu H, Isola J (2014) Trastuzumab emtansine: mechanisms of action and drug resistance. Breast Cancer Res BCR 16(2):209. doi:10.1186/bcr3621

    Article  PubMed  Google Scholar 

  10. Rowinsky EK, Donehower RC (1995) Paclitaxel (taxol). N Engl J Med 332(15):1004–1014. doi:10.1056/NEJM199504133321507

    Article  CAS  PubMed  Google Scholar 

  11. Rowinsky EK, Eisenhauer EA, Chaudhry V, Arbuck SG, Donehower RC (1993) Clinical toxicities encountered with paclitaxel (Taxol). Semin Oncol 20(4 Suppl 3):1–15

    CAS  PubMed  Google Scholar 

  12. Manfredi JJ, Horwitz SB (1984) Vinblastine paracrystals from cultured cells are calcium-stable. Exp Cell Res 150(1):205–212

    Article  CAS  PubMed  Google Scholar 

  13. Nogales E, Wolf SG, Downing KH (1998) Structure of the alpha beta tubulin dimer by electron crystallography. Nature 391(6663):199–203. doi:10.1038/34465

    Article  CAS  PubMed  Google Scholar 

  14. Yusuf RZ, Duan Z, Lamendola DE, Penson RT, Seiden MV (2003) Paclitaxel resistance: molecular mechanisms and pharmacologic manipulation. Curr Cancer Drug Targets 3(1):1–19

    Article  CAS  PubMed  Google Scholar 

  15. Huang Y, Ibrado AM, Reed JC, Bullock G, Ray S, Tang C, Bhalla K (1997) Co-expression of several molecular mechanisms of multidrug resistance and their significance for paclitaxel cytotoxicity in human AML HL-60 cells. Leukemia 11(2):253–257

    Article  CAS  PubMed  Google Scholar 

  16. Jang SH, Wientjes MG, Au JL (2001) Kinetics of P-glycoprotein-mediated efflux of paclitaxel. J Pharmacol Exp Ther 298(3):1236–1242

    CAS  PubMed  Google Scholar 

  17. Mozzetti S, Ferlini C, Concolino P, Filippetti F, Raspaglio G, Prislei S, Gallo D, Martinelli E, Ranelletti FO, Ferrandina G, Scambia G (2005) Class III beta-tubulin overexpression is a prominent mechanism of paclitaxel resistance in ovarian cancer patients. Clin Cancer Res 11(1):298–305

    CAS  PubMed  Google Scholar 

  18. Gazitt Y, Rothenberg ML, Hilsenbeck SG, Fey V, Thomas C, Montegomrey W (1998) Bcl-2 overexpression is associated with resistance to paclitaxel, but not gemcitabine, in multiple myeloma cells. Int J Oncol 13(4):839–848

    CAS  PubMed  Google Scholar 

  19. Liu JR, Fletcher B, Page C, Hu C, Nunez G, Baker V (1998) Bcl-xL is expressed in ovarian carcinoma and modulates chemotherapy-induced apoptosis. Gynecol Oncol 70(3):398–403. doi:10.1006/gyno.1998.5125

    Article  CAS  PubMed  Google Scholar 

  20. Panvichian R, Orth K, Day ML, Day KC, Pilat MJ, Pienta KJ (1998) Paclitaxel-associated multimininucleation is permitted by the inhibition of caspase activation: a potential early step in drug resistance. Can Res 58(20):4667–4672

    CAS  Google Scholar 

  21. Amos LA, Schlieper D (2005) Microtubules and maps. Adv Protein Chem 71:257–298. doi:10.1016/S0065-3233(04)71007-4

    Article  CAS  PubMed  Google Scholar 

  22. Yang Y, Liu M, Li D, Ran J, Gao J, Suo S, Sun SC, Zhou J (2014) CYLD regulates spindle orientation by stabilizing astral microtubules and promoting dishevelled-NuMA-dynein/dynactin complex formation. Proc Natl Acad Sci USA 111(6):2158–2163. doi:10.1073/pnas.1319341111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gao J, Huo L, Sun X, Liu M, Li D, Dong JT, Zhou J (2008) The tumor suppressor CYLD regulates microtubule dynamics and plays a role in cell migration. J Biol Chem 283(14):8802–8809. doi:10.1074/jbc.M708470200

    Article  CAS  PubMed  Google Scholar 

  24. Li D, Gao J, Yang Y, Sun L, Suo S, Luo Y, Shui W, Zhou J, Liu M (2014) CYLD coordinates with EB1 to regulate microtubule dynamics and cell migration. Cell Cycle 13(6):974–983. doi:10.4161/cc.27838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Etienne-Manneville S (2010) From signaling pathways to microtubule dynamics: the key players. Curr Opin Cell Biol 22(1):104–111. doi:10.1016/j.ceb.2009.11.008

    Article  CAS  PubMed  Google Scholar 

  26. Simeonov DR, Kenny K, Seo L, Moyer A, Allen J, Paluh JL (2009) Distinct Kinesin-14 mitotic mechanisms in spindle bipolarity. Cell Cycle 8(21):3571–3583. doi:10.4161/cc.8.21.9970

    Article  CAS  PubMed  Google Scholar 

  27. Glotzer M (2009) The 3Ms of central spindle assembly: microtubules, motors and MAPs. Nat Rev Mol Cell Biol 10(1):9–20. doi:10.1038/nrm2609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sun L, Gao J, Dong X, Liu M, Li D, Shi X, Dong JT, Lu X, Liu C, Zhou J (2008) EB1 promotes Aurora-B kinase activity through blocking its inactivation by protein phosphatase 2A. Proc Natl Acad Sci USA 105(20):7153–7158. doi:10.1073/pnas.0710018105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Dong X, Liu F, Sun L, Liu M, Li D, Su D, Zhu Z, Dong JT, Fu L, Zhou J (2010) Oncogenic function of microtubule end-binding protein 1 in breast cancer. J Pathol 220(3):361–369. doi:10.1002/path.2662

    CAS  PubMed  Google Scholar 

  30. Rouzier R, Rajan R, Wagner P, Hess KR, Gold DL, Stec J, Ayers M, Ross JS, Zhang P, Buchholz TA, Kuerer H, Green M, Arun B, Hortobagyi GN, Symmans WF, Pusztai L (2005) Microtubule-associated protein tau: a marker of paclitaxel sensitivity in breast cancer. Proc Natl Acad Sci USA 102(23):8315–8320. doi:10.1073/pnas.0408974102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Sun X, Li D, Yang Y, Ren Y, Li J, Wang Z, Dong B, Liu M, Zhou J (2012) Microtubule-binding protein CLIP-170 is a mediator of paclitaxel sensitivity. J Pathol 226(4):666–673. doi:10.1002/path.3026

    Article  CAS  PubMed  Google Scholar 

  32. Drechsel DN, Hyman AA, Cobb MH, Kirschner MW (1992) Modulation of the dynamic instability of tubulin assembly by the microtubule-associated protein tau. Mol Biol Cell 3(10):1141–1154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Robert M, Mathuranath PS (2007) Tau and tauopathies. Neurol India 55(1):11–16

    Article  CAS  PubMed  Google Scholar 

  34. Wagner P, Wang B, Clark E, Lee H, Rouzier R, Pusztai L (2005) Microtubule Associated Protein (MAP)-Tau: a novel mediator of paclitaxel sensitivity in vitro and in vivo. Cell Cycle 4(9):1149–1152. doi:10.4161/cc.4.9.2038

    Article  CAS  PubMed  Google Scholar 

  35. Tanaka S, Nohara T, Iwamoto M, Sumiyoshi K, Kimura K, Takahashi Y, Tanigawa N (2009) Tau expression and efficacy of paclitaxel treatment in metastatic breast cancer. Cancer Chemother Pharmacol 64(2):341–346. doi:10.1007/s00280-008-0877-5

    Article  CAS  PubMed  Google Scholar 

  36. Gurler H, Yu Y, Choi J, Kajdacsy-Balla AA, Barbolina MV (2015) Three-dimensional collagen type I matrix up-regulates nuclear isoforms of the microtubule associated protein tau implicated in resistance to paclitaxel therapy in ovarian carcinoma. Int J Mol Sci 16(2):3419–3433. doi:10.3390/ijms16023419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Blumcke I, Muller S, Buslei R, Riederer BM, Wiestler OD (2004) Microtubule-associated protein-2 immunoreactivity: a useful tool in the differential diagnosis of low-grade neuroepithelial tumors. Acta Neuropathol 108(2):89–96. doi:10.1007/s00401-004-0873-8

    Article  PubMed  CAS  Google Scholar 

  38. Chen JY, Chang YL, Yu YC, Chao CC, Kao HW, Wu CT, Lin WC, Ko JY, Jou YS (2004) Specific induction of the high-molecular-weight microtubule-associated protein 2 (hmw-MAP2) by betel quid extract in cultured oral keratinocytes: clinical implications in betel quid-associated oral squamous cell carcinoma (OSCC). Carcinogenesis 25(2):269–276. doi:10.1093/carcin/bgh006

    Article  CAS  PubMed  Google Scholar 

  39. Liu Y, Mangini J, Saad R, Silverman AR, Abell E, Tung MY, Graner SR, Silverman JF (2003) Diagnostic value of microtubule-associated protein-2 in Merkel cell carcinoma. Appl Immunohistochem Mol Morphol AIMM 11(4):326–329

    Article  CAS  PubMed  Google Scholar 

  40. Liu Y, Sturgis CD, Grzybicki DM, Jasnosz KM, Olson PR, Tong M, Dabbs DD, Raab SS, Silverman JF (2001) Microtubule-associated protein-2: a new sensitive and specific marker for pulmonary carcinoid tumor and small cell carcinoma. Mod Pathol 14(9):880–885. doi:10.1038/modpathol.3880406

    Article  CAS  PubMed  Google Scholar 

  41. Soltani MH, Pichardo R, Song Z, Sangha N, Camacho F, Satyamoorthy K, Sangueza OP, Setaluri V (2005) Microtubule-associated protein 2, a marker of neuronal differentiation, induces mitotic defects, inhibits growth of melanoma cells, and predicts metastatic potential of cutaneous melanoma. Am J Pathol 166(6):1841–1850. doi:10.1016/S0002-9440(10)62493-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Bauer JA, Chakravarthy AB, Rosenbluth JM, Mi D, Seeley EH, De Matos Granja-Ingram N, Olivares MG, Kelley MC, Mayer IA, Meszoely IM, Means-Powell JA, Johnson KN, Tsai CJ, Ayers GD, Sanders ME, Schneider RJ, Formenti SC, Caprioli RM, Pietenpol JA (2010) Identification of markers of taxane sensitivity using proteomic and genomic analyses of breast tumors from patients receiving neoadjuvant paclitaxel and radiation. Clin Cancer Res 16(2):681–690. doi:10.1158/1078-0432.CCR-09-1091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sun X, Shi X, Liu M, Li D, Zhang L, Liu X, Zhou J (2011) Mdp3 is a novel microtubule-binding protein that regulates microtubule assembly and stability. Cell Cycle 10(22):3929–3937. doi:10.4161/cc.10.22.18106

    Article  CAS  PubMed  Google Scholar 

  44. Howard J, Hyman AA (2003) Dynamics and mechanics of the microtubule plus end. Nature 422(6933):753–758. doi:10.1038/nature01600

    Article  CAS  PubMed  Google Scholar 

  45. 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):309–322. doi:10.1038/nrm2369

    Article  CAS  PubMed  Google Scholar 

  46. Honnappa S, Okhrimenko O, Jaussi R, Jawhari H, Jelesarov I, Winkler FK, Steinmetz MO (2006) Key interaction modes of dynamic +TIP networks. Mol Cell 23(5):663–671. doi:10.1016/j.molcel.2006.07.013

    Article  CAS  PubMed  Google Scholar 

  47. Komarova Y, Lansbergen G, Galjart N, Grosveld F, Borisy GG, Akhmanova A (2005) EB1 and EB3 control CLIP dissociation from the ends of growing microtubules. Mol Biol Cell 16(11):5334–5345. doi:10.1091/mbc.E05-07-0614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Askham JM, Vaughan KT, Goodson HV, Morrison EE (2002) Evidence that an interaction between EB1 and p150(Glued) is required for the formation and maintenance of a radial microtubule array anchored at the centrosome. Mol Biol Cell 13(10):3627–3645. doi:10.1091/mbc.E02-01-0061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Dixit R, Barnett B, Lazarus JE, Tokito M, Goldman YE, Holzbaur EL (2009) Microtubule plus-end tracking by CLIP-170 requires EB1. Proc Natl Acad Sci USA 106(2):492–497. doi:10.1073/pnas.0807614106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Su LK, Qi Y (2001) Characterization of human MAPRE genes and their proteins. Genomics 71(2):142–149. doi:10.1006/geno.2000.6428

    Article  CAS  PubMed  Google Scholar 

  51. Xie S, Ogden A, Aneja R, Zhou J (2016) Microtubule-binding proteins as promising biomarkers of paclitaxel sensitivity in cancer chemotherapy. Med Res Rev 36(2):300–312. doi:10.1002/med.21378

    Article  CAS  PubMed  Google Scholar 

  52. Komarova Y, De Groot CO, Grigoriev I, Gouveia SM, Munteanu EL, Schober JM, Honnappa S, Buey RM, Hoogenraad CC, Dogterom M, Borisy GG, Steinmetz MO, Akhmanova A (2009) Mammalian end binding proteins control persistent microtubule growth. J Cell Biol 184(5):691–706. doi:10.1083/jcb.200807179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Tirnauer JS, Grego S, Salmon ED, Mitchison TJ (2002) EB1-microtubule interactions in Xenopus egg extracts: role of EB1 in microtubule stabilization and mechanisms of targeting to microtubules. Mol Biol Cell 13(10):3614–3626. doi:10.1091/mbc.E02-04-0210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Manna T, Honnappa S, Steinmetz MO, Wilson L (2008) Suppression of microtubule dynamic instability by the +TIP protein EB1 and its modulation by the CAP-Gly domain of p150glued. Biochemistry 47(2):779–786. doi:10.1021/bi701912g

    Article  CAS  PubMed  Google Scholar 

  55. Vitre B, Coquelle FM, Heichette C, Garnier C, Chretien D, Arnal I (2008) EB1 regulates microtubule dynamics and tubulin sheet closure in vitro. Nat Cell Biol 10(4):415–421. doi:10.1038/ncb1703

    Article  CAS  PubMed  Google Scholar 

  56. Luo Y, Li D, Ran J, Yan B, Chen J, Dong X, Liu Z, Liu R, Zhou J, Liu M (2014) End-binding protein 1 stimulates paclitaxel sensitivity in breast cancer by promoting its actions toward microtubule assembly and stability. Protein Cell 5(6):469–479. doi:10.1007/s13238-014-0053-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Thomas GE, Sreeja JS, Gireesh KK, Gupta H, Manna TK (2015) +TIP EB1 downregulates paclitaxel-induced proliferation inhibition and apoptosis in breast cancer cells through inhibition of paclitaxel binding on microtubules. Int J Oncol 46(1):133–146. doi:10.3892/ijo.2014.2701

    Article  CAS  PubMed  Google Scholar 

  58. Honnappa S, Gouveia SM, Weisbrich A, Damberger FF, Bhavesh NS, Jawhari H, Grigoriev I, van Rijssel FJ, Buey RM, Lawera A, Jelesarov I, Winkler FK, Wuthrich K, Akhmanova A, Steinmetz MO (2009) An EB1-binding motif acts as a microtubule tip localization signal. Cell 138(2):366–376. doi:10.1016/j.cell.2009.04.065

    Article  CAS  PubMed  Google Scholar 

  59. Luders J, Stearns T (2007) Microtubule-organizing centres: a re-evaluation. Nat Rev Mol Cell Biol 8(2):161–167. doi:10.1038/nrm2100

    Article  PubMed  CAS  Google Scholar 

  60. Tanenbaum ME, Medema RH (2010) Mechanisms of centrosome separation and bipolar spindle assembly. Dev Cell 19(6):797–806. doi:10.1016/j.devcel.2010.11.011

    Article  CAS  PubMed  Google Scholar 

  61. O’Connell CB, Khodjakov AL (2007) Cooperative mechanisms of mitotic spindle formation. J Cell Sci 120(Pt 10):1717–1722. doi:10.1242/jcs.03442

    Article  PubMed  CAS  Google Scholar 

  62. Nigg EA (2002) Centrosome aberrations: cause or consequence of cancer progression? Nat Rev Cancer 2(11):815–825. doi:10.1038/nrc924

    Article  CAS  PubMed  Google Scholar 

  63. Brinkley BR (2001) Managing the centrosome numbers game: from chaos to stability in cancer cell division. Trends Cell Biol 11(1):18–21

    Article  CAS  PubMed  Google Scholar 

  64. Lingle WL, Barrett SL, Negron VC, D’Assoro AB, Boeneman K, Liu W, Whitehead CM, Reynolds C, Salisbury JL (2002) Centrosome amplification drives chromosomal instability in breast tumor development. Proc Natl Acad Sci USA 99(4):1978–1983. doi:10.1073/pnas.032479999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Godinho SA, Pellman D (2014) Causes and consequences of centrosome abnormalities in cancer. Philos Trans R Soc Lond Ser B Biol Sci 369(1650):20130467. doi:10.1098/rstb.2013.0467

    Article  CAS  Google Scholar 

  66. Rida PC, Cantuaria G, Reid MD, Kucuk O, Aneja R (2015) How to be good at being bad: centrosome amplification and mitotic propensity drive intratumoral heterogeneity. Cancer Metastasis Rev 34(4):703–713. doi:10.1007/s10555-015-9590-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Pannu V, Mittal K, Cantuaria G, Reid MD, Li X, Donthamsetty S, McBride M, Klimov S, Osan R, Gupta MV, Rida PC, Aneja R (2015) Rampant centrosome amplification underlies more aggressive disease course of triple negative breast cancers. Oncotarget 6(12):10487–10497. doi:10.18632/oncotarget.3402

    Article  PubMed  PubMed Central  Google Scholar 

  68. Liu L, Zou P, Zhang M, Tian L, Liu F (2006) Effect of polo-like kinase 1 gene silence on cell cycle and drug resistance in K562/A02 cell. Chin Med J 119(7):605–608

    CAS  PubMed  Google Scholar 

  69. Ro S, Yang LX (2004) Centrosomes–their role in tumors and cancer therapy. Anticancer Res 24(5B):3269–3273

    PubMed  Google Scholar 

  70. 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):51–62

    Article  CAS  PubMed  Google Scholar 

  71. Casenghi M, Meraldi P, Weinhart U, Duncan PI, Korner R, Nigg EA (2003) Polo-like kinase 1 regulates Nlp, a centrosome protein involved in microtubule nucleation. Dev Cell 5(1):113–125

    Article  CAS  PubMed  Google Scholar 

  72. Zhao W, Song Y, Xu B, Zhan Q (2012) Overexpression of centrosomal protein Nlp confers breast carcinoma resistance to paclitaxel. Cancer Biol Ther 13(3):156–163. doi:10.4161/cbt.13.3.18697

    Article  CAS  PubMed  Google Scholar 

  73. Shao S, Liu R, Wang Y, Song Y, Zuo L, Xue L, Lu N, Hou N, Wang M, Yang X, Zhan Q (2010) Centrosomal Nlp is an oncogenic protein that is gene-amplified in human tumors and causes spontaneous tumorigenesis in transgenic mice. J Clin Investig 120(2):498–507. doi:10.1172/JCI39447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Qu D, Qu H, Fu M, Zhao X, Liu R, Sui L, Zhan Q (2008) Increased expression of Nlp, a potential oncogene in ovarian cancer, and its implication in carcinogenesis. Gynecol Oncol 110(2):230–236. doi:10.1016/j.ygyno.2008.04.015

    Article  CAS  PubMed  Google Scholar 

  75. Gergely F (2002) Centrosomal TACCtics. BioEssays News Rev Mol Cell Dev Biol 24(10):915–925. doi:10.1002/bies.10162

    Article  CAS  Google Scholar 

  76. Gergely F, Draviam VM, Raff JW (2003) The ch-TOG/XMAP215 protein is essential for spindle pole organization in human somatic cells. Genes Dev 17(3):336–341. doi:10.1101/gad.245603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. 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):1580–1590. doi:10.1091/mbc.E03-07-0544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Schneider L, Essmann F, Kletke A, Rio P, Hanenberg H, Wetzel W, Schulze-Osthoff K, Nurnberg B, Piekorz RP (2007) The transforming acidic coiled coil 3 protein is essential for spindle-dependent chromosome alignment and mitotic survival. J Biol Chem 282(40):29273–29283. doi:10.1074/jbc.M704151200

    Article  CAS  PubMed  Google Scholar 

  79. Yao R, Natsume Y, Noda T (2007) TACC3 is required for the proper mitosis of sclerotome mesenchymal cells during formation of the axial skeleton. Cancer Sci 98(4):555–562. doi:10.1111/j.1349-7006.2007.00433.x

    Article  CAS  PubMed  Google Scholar 

  80. Ha GH, Kim JL, Breuer EK (2013) Transforming acidic coiled-coil proteins (TACCs) in human cancer. Cancer Lett 336(1):24–33. doi:10.1016/j.canlet.2013.04.022

    Article  CAS  PubMed  Google Scholar 

  81. Cully M, Shiu J, Piekorz RP, Muller WJ, Done SJ, Mak TW (2005) Transforming acidic coiled coil 1 promotes transformation and mammary tumorigenesis. Can Res 65(22):10363–10370. doi:10.1158/0008-5472.CAN-05-1633

    Article  CAS  Google Scholar 

  82. Lv J, Yao YS, Zhou F, Zhuang LK, Yao RY, Liang J, Qiu WS, Yue L (2014) Prognosis significance of HER2 status and TACC1 expression in patients with gastric carcinoma. Med Oncol 31(11):280. doi:10.1007/s12032-014-0280-5

    Article  PubMed  CAS  Google Scholar 

  83. Onodera Y, Takagi K, Miki Y, Takayama K, Shibahara Y, Watanabe M, Ishida T, Inoue S, Sasano H, Suzuki T (2016) TACC2 (transforming acidic coiled-coil protein 2) in breast carcinoma as a potent prognostic predictor associated with cell proliferation. Cancer Med 5(8):1973–1982. doi:10.1002/cam4.736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Lauffart B, Vaughan MM, Eddy R, Chervinsky D, DiCioccio RA, Black JD, Still IH (2005) Aberrations of TACC1 and TACC3 are associated with ovarian cancer. BMC Women’s Health 5:8. doi:10.1186/1472-6874-5-8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Jung CK, Jung JH, Park GS, Lee A, Kang CS, Lee KY (2006) Expression of transforming acidic coiled-coil containing protein 3 is a novel independent prognostic marker in non-small cell lung cancer. Pathol Int 56(9):503–509. doi:10.1111/j.1440-1827.2006.01998.x

    Article  CAS  PubMed  Google Scholar 

  86. Kiemeney LA, Sulem P, Besenbacher S, Vermeulen SH, Sigurdsson A, Thorleifsson G, Gudbjartsson DF, Stacey SN, Gudmundsson J, Zanon C, Kostic J, Masson G, Bjarnason H, Palsson ST, Skarphedinsson OB, Gudjonsson SA, Witjes JA, Grotenhuis AJ, Verhaegh GW, Bishop DT, Sak SC, Choudhury A, Elliott F, Barrett JH, Hurst CD, de Verdier PJ, Ryk C, Rudnai P, Gurzau E, Koppova K, Vineis P, Polidoro S, Guarrera S, Sacerdote C, Campagna M, Placidi D, Arici C, Zeegers MP, Kellen E, Gutierrez BS, Sanz-Velez JI, Sanchez-Zalabardo M, Valdivia G, Garcia-Prats MD, Hengstler JG, Blaszkewicz M, Dietrich H, Ophoff RA, van den Berg LH, Alexiusdottir K, Kristjansson K, Geirsson G, Nikulasson S, Petursdottir V, Kong A, Thorgeirsson T, Mungan NA, Lindblom A, van Es MA, Porru S, Buntinx F, Golka K, Mayordomo JI, Kumar R, Matullo G, Steineck G, Kiltie AE, Aben KK, Jonsson E, Thorsteinsdottir U, Knowles MA, Rafnar T, Stefansson K (2010) A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer. Nat Genet 42(5):415–419. doi:10.1038/ng.558

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Schmidt S, Schneider L, Essmann F, Cirstea IC, Kuck F, Kletke A, Janicke RU, Wiek C, Hanenberg H, Ahmadian MR, Schulze-Osthoff K, Nurnberg B, Piekorz RP (2010) The centrosomal protein TACC3 controls paclitaxel sensitivity by modulating a premature senescence program. Oncogene 29(46):6184–6192. doi:10.1038/onc.2010.354

    Article  CAS  PubMed  Google Scholar 

  88. Ahmed AA, Lu Z, Jennings NB, Etemadmoghadam D, Capalbo L, Jacamo RO, Barbosa-Morais N, Le XF, Australian Ovarian Cancer Study G, Vivas-Mejia P, Lopez-Berestein G, Grandjean G, Bartholomeusz G, Liao W, Andreeff M, Bowtell D, Glover DM, Sood Jr AK, Bast RC (2010) SIK2 is a centrosome kinase required for bipolar mitotic spindle formation that provides a potential target for therapy in ovarian cancer. Cancer Cell 18(2):109–121. doi:10.1016/j.ccr.2010.06.018

    Article  CAS  PubMed  Google Scholar 

  89. Fry AM, Mayor T, Meraldi P, Stierhof YD, Tanaka K, Nigg EA (1998) C-Nap1, a novel centrosomal coiled-coil protein and candidate substrate of the cell cycle-regulated protein kinase Nek2. J Cell Biol 141(7):1563–1574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Mayor T, Hacker U, Stierhof YD, Nigg EA (2002) The mechanism regulating the dissociation of the centrosomal protein C-Nap1 from mitotic spindle poles. J Cell Sci 115(Pt 16):3275–3284

    CAS  PubMed  Google Scholar 

  91. Shi X, Liu M, Li D, Wang J, Aneja R, Zhou J (2012) Cep70 contributes to angiogenesis by modulating microtubule rearrangement and stimulating cell polarization and migration. Cell Cycle 11(8):1554–1563. doi:10.4161/cc.19954

    Article  CAS  PubMed  Google Scholar 

  92. Shi X, Sun X, Liu M, Li D, Aneja R, Zhou J (2011) CEP70 protein interacts with gamma-tubulin to localize at the centrosome and is critical for mitotic spindle assembly. J Biol Chem 286(38):33401–33408. doi:10.1074/jbc.M111.252262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Shi X, Wang J, Yang Y, Ren Y, Zhou J, Li D (2012) Cep70 promotes microtubule assembly in vitro by increasing microtubule elongation. Acta Biochim Biophys Sin 44(5):450–454. doi:10.1093/abbs/gms017

    Article  CAS  PubMed  Google Scholar 

  94. Shi X, Yao Y, Wang Y, Zhang Y, Huang Q, Zhou J, Liu M, Li D (2015) Cep70 regulates microtubule stability by interacting with HDAC6. FEBS Lett 589(15):1771–1777. doi:10.1016/j.febslet.2015.06.017

    Article  CAS  PubMed  Google Scholar 

  95. Shi X, Wang Y, Sun X, Wang C, Jiang P, Zhang Y, Huang Q, Liu X, Li D, Zhou J, Liu M (2017) Centrosomal protein 70 is a mediator of paclitaxel sensitivity. Int J Mol Sci 18(6):1267. doi:10.3390/ijms18061267

    Article  PubMed Central  Google Scholar 

  96. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70

    Article  CAS  PubMed  Google Scholar 

  97. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. doi:10.1016/j.cell.2011.02.013

    Article  CAS  PubMed  Google Scholar 

  98. Kops GJ, Weaver BA, Cleveland DW (2005) On the road to cancer: aneuploidy and the mitotic checkpoint. Nat Rev Cancer 5(10):773–785. doi:10.1038/nrc1714

    Article  CAS  PubMed  Google Scholar 

  99. Fang X, Zhang P (2011) Aneuploidy and tumorigenesis. Semin Cell Dev Biol 22(6):595–601. doi:10.1016/j.semcdb.2011.03.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Lara-Gonzalez P, Westhorpe FG, Taylor SS (2012) The spindle assembly checkpoint. Curr Biol CB 22(22):R966–R980. doi:10.1016/j.cub.2012.10.006

    Article  CAS  PubMed  Google Scholar 

  101. Prencipe M, Fitzpatrick P, Gorman S, Tosetto M, Klinger R, Furlong F, Harrison M, O’Connor D, Roninson IB, O’Sullivan J, McCann A (2009) Cellular senescence induced by aberrant MAD2 levels impacts on paclitaxel responsiveness in vitro. Br J Cancer 101(11):1900–1908. doi:10.1038/sj.bjc.6605419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Bargiela-Iparraguirre J, Prado-Marchal L, Pajuelo-Lozano N, Jimenez B, Perona R, Sanchez-Perez I (2014) Mad2 and BubR1 modulates tumourigenesis and paclitaxel response in MKN45 gastric cancer cells. Cell Cycle 13(22):3590–3601. doi:10.4161/15384101.2014.962952

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Fu Y, Ye D, Chen H, Lu W, Ye F, Xie X (2007) Weakened spindle checkpoint with reduced BubR1 expression in paclitaxel-resistant ovarian carcinoma cell line SKOV3-TR30. Gynecol Oncol 105(1):66–73. doi:10.1016/j.ygyno.2006.10.061

    Article  CAS  PubMed  Google Scholar 

  104. Hirokawa N, Noda Y (2008) Intracellular transport and kinesin superfamily proteins, KIFs: structure, function, and dynamics. Physiol Rev 88(3):1089–1118. doi:10.1152/physrev.00023.2007

    Article  CAS  PubMed  Google Scholar 

  105. Miki H, Setou M, Kaneshiro K, Hirokawa N (2001) All kinesin superfamily protein, KIF, genes in mouse and human. Proc Natl Acad Sci USA 98(13):7004–7011. doi:10.1073/pnas.111145398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Hirokawa N (1998) Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science 279(5350):519–526

    Article  CAS  PubMed  Google Scholar 

  107. Rath O, Kozielski F (2012) Kinesins and cancer. Nat Rev Cancer 12(8):527–539. doi:10.1038/nrc3310

    Article  CAS  PubMed  Google Scholar 

  108. Yu Y, Feng YM (2010) The role of kinesin family proteins in tumorigenesis and progression: potential biomarkers and molecular targets for cancer therapy. Cancer 116(22):5150–5160. doi:10.1002/cncr.25461

    Article  CAS  PubMed  Google Scholar 

  109. Miki H, Okada Y, Hirokawa N (2005) Analysis of the kinesin superfamily: insights into structure and function. Trends Cell Biol 15(9):467–476. doi:10.1016/j.tcb.2005.07.006

    Article  CAS  PubMed  Google Scholar 

  110. Tan MH, De S, Bebek G, Orloff MS, Wesolowski R, Downs-Kelly E, Budd GT, Stark GR, Eng C (2012) Specific kinesin expression profiles associated with taxane resistance in basal-like breast cancer. Breast Cancer Res Treat 131(3):849–858. doi:10.1007/s10549-011-1500-8

    Article  CAS  PubMed  Google Scholar 

  111. Wang W, Shi Y, Li J, Cui W, Yang B (2016) Up-regulation of KIF14 is a predictor of poor survival and a novel prognostic biomarker of chemoresistance to paclitaxel treatment in cervical cancer. Biosci Rep 36(2):e00315. doi:10.1042/BSR20150314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by Grants from the National Natural Science Foundation of China (31301113 and 31601089), the Natural Science Foundation of Jiangsu Province (BK20130607), and the Fundamental Research Funds for the Central Universities. Xingjuan Shi was supported by a scholarship from the China Scholarship Council.

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  1. Key Laboratory of Developmental Genes and Human Disease, Institute of Life Sciences, Southeast University, Nanjing, 210096, China

    Xingjuan Shi

  2. School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, 510006, China

    Xiaoou Sun

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  1. Xingjuan Shi
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  2. Xiaoou Sun
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XS and XS designed the study and wrote the paper. All authors read and approved the final manuscript.

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Correspondence to Xingjuan Shi or Xiaoou Sun.

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Shi, X., Sun, X. Regulation of paclitaxel activity by microtubule-associated proteins in cancer chemotherapy. Cancer Chemother Pharmacol 80, 909–917 (2017). https://doi.org/10.1007/s00280-017-3398-2

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