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Centrosome amplification: a quantifiable cancer cell trait with prognostic value in solid malignancies

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Abstract

Numerical and/or structural centrosome amplification (CA) is a hallmark of cancers that is often associated with the aberrant tumor karyotypes and poor clinical outcomes. Mechanistically, CA compromises mitotic fidelity and leads to chromosome instability (CIN), which underlies tumor initiation and progression. Recent technological advances in microscopy and image analysis platforms have enabled better-than-ever detection and quantification of centrosomal aberrancies in cancer. Numerous studies have thenceforth correlated the presence and the degree of CA with indicators of poor prognosis such as higher tumor grade and ability to recur and metastasize. We have pioneered a novel semi-automated pipeline that integrates immunofluorescence confocal microscopy with digital image analysis to yield a quantitative centrosome amplification score (CAS), which is a summation of the severity and frequency of structural and numerical centrosome aberrations in tumor samples. Recent studies in breast cancer show that CA increases across the disease progression continuum, while normal breast tissue exhibited the lowest CA, followed by cancer-adjacent apparently normal, ductal carcinoma in situ and invasive tumors, which showed the highest CA. This finding strengthens the notion that CA could be evolutionarily favored and can promote tumor progression and metastasis. In this review, we discuss the prevalence, extent, and severity of CA in various solid cancer types, the utility of quantifying amplified centrosomes as an independent prognostic marker. We also highlight the clinical feasibility of a CA-based risk score for predicting recurrence, metastasis, and overall prognosis in patients with solid cancers.

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References

  1. Hamoir, G. (1992). The discovery of meiosis by E. van Beneden, a breakthrough in the morphological phase of heredity. The International Journal of Developmental Biology, 36(1), 9–15.

    CAS  PubMed  Google Scholar 

  2. van Beneden, E., & A, N. (1887). Nouvelle recherches sur la fécondation et la division mitosique chez l’Ascaride mégalocéphale. Bulletin de l'Académie Royale des Sciences 3éme sér., 14, 215–295.

  3. Scheer, U. (2014). Historical roots of centrosome research: discovery of Boveri’s microscope slides in Wurzburg. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 369(1650). https://doi.org/10.1098/rstb.2013.0469.

  4. Yang, E. C., Schwarz, R. A., Lang, A. K., Bass, N., Badaoui, H., Vohra, I. S., et al. (2018). In vivo multimodal optical imaging: improved detection of oral dysplasia in low-risk oral mucosal lesions. Cancer Prevention Research (Philadelphia, Pa.), 11(8), 465–476. https://doi.org/10.1158/1940-6207.CAPR-18-0032.

    Article  Google Scholar 

  5. Boveri, T. (1887). Ueber den Antheil des Spermatozoon an der Teilung des Eies. Sitzungsber Ges Morph Physiol München 3, 151–164.

  6. Salisbury, J. L. (2004). Centrosomes: Sfi1p and centrin unravel a structural riddle. Current Biology, 14(1), R27–R29. https://doi.org/10.1016/j.cub.2003.12.019.

    Article  CAS  PubMed  Google Scholar 

  7. Doxsey, S. J., Stein, P., Evans, L., Calarco, P. D., & Kirschner, M. (1994). Pericentrin, a highly conserved centrosome protein involved in microtubule organization. Cell, 76(4), 639–650. https://doi.org/10.1016/0092-8674(94)90504-5.

    Article  CAS  PubMed  Google Scholar 

  8. Kirschner, M., & Mitchison, T. (1986). Beyond self-assembly: from microtubules to morphogenesis. Cell, 45(3), 329–342. https://doi.org/10.1016/0092-8674(86)90318-1.

    Article  CAS  PubMed  Google Scholar 

  9. Hinchcliffe, E. H., Miller, F. J., Cham, M., Khodjakov, A., & Sluder, G. (2001). Requirement of a centrosomal activity for cell cycle progression through G1 into S phase. Science, 291(5508), 1547–1550. https://doi.org/10.1126/science.1056866.

    Article  CAS  PubMed  Google Scholar 

  10. Pihan, G. A., Purohit, A., Wallace, J., Knecht, H., Woda, B., Quesenberry, P., et al. (1998). Centrosome defects and genetic instability in malignant tumors. Cancer Research, 58(17), 3974–3985.

    CAS  PubMed  Google Scholar 

  11. Kawamura, K., Moriyama, M., Shiba, N., Ozaki, M., Tanaka, T., Nojima, T., et al. (2003). Centrosome hyperamplification and chromosomal instability in bladder cancer. European Urology, 43(5), 505–515. https://doi.org/10.1016/s0302-2838(03)00056-3.

    Article  CAS  PubMed  Google Scholar 

  12. Denu, R. A., Zasadil, L. M., Kanugh, C., Laffin, J., Weaver, B. A., & Burkard, M. E. (2016). Centrosome amplification induces high grade features and is prognostic of worse outcomes in breast cancer. BMC Cancer, 16, 47. https://doi.org/10.1186/s12885-016-2083-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Shimomura, A., Miyoshi, Y., Taguchi, T., Tamaki, Y., & Noguchi, S. (2009). Association of loss of BRCA1 expression with centrosome aberration in human breast cancer. Journal of Cancer Research and Clinical Oncology, 135(3), 421–430. https://doi.org/10.1007/s00432-008-0472-5.

    Article  CAS  PubMed  Google Scholar 

  14. Giehl, M., Fabarius, A., Frank, O., Hochhaus, A., Hafner, M., Hehlmann, R., et al. (2005). Centrosome aberrations in chronic myeloid leukemia correlate with stage of disease and chromosomal instability. Leukemia, 19(7), 1192–1197. https://doi.org/10.1038/sj.leu.2403779.

    Article  CAS  PubMed  Google Scholar 

  15. Holland, A. J., Lan, W., & Cleveland, D. W. (2010). Centriole duplication: a lesson in self-control. Cell Cycle, 9(14), 2731–2736. https://doi.org/10.4161/cc.9.14.12184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Loncarek, J., & Khodjakov, A. (2009). Ab ovo or de novo? Mechanisms of centriole duplication. Molecules and Cells, 27(2), 135–142. https://doi.org/10.1007/s10059-009-0017-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Tsou, M. F., & Stearns, T. (2006). Mechanism limiting centrosome duplication to once per cell cycle. Nature, 442(7105), 947–951. https://doi.org/10.1038/nature04985.

    Article  CAS  PubMed  Google Scholar 

  18. Vader, G., & Lens, S. M. (2008). The Aurora kinase family in cell division and cancer. Biochimica et Biophysica Acta, 1786(1), 60–72. https://doi.org/10.1016/j.bbcan.2008.07.003.

    Article  CAS  PubMed  Google Scholar 

  19. Cizmecioglu, O., Arnold, M., Bahtz, R., Settele, F., Ehret, L., Haselmann-Weiss, U., et al. (2010). Cep152 acts as a scaffold for recruitment of Plk4 and CPAP to the centrosome. The Journal of Cell Biology, 191(4), 731–739. https://doi.org/10.1083/jcb.201007107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Habedanck, R., Stierhof, Y. D., Wilkinson, C. J., & Nigg, E. A. (2005). The Polo kinase Plk4 functions in centriole duplication. Nature Cell Biology, 7(11), 1140–1146. https://doi.org/10.1038/ncb1320.

    Article  CAS  PubMed  Google Scholar 

  21. Loffler, H., Fechter, A., Matuszewska, M., Saffrich, R., Mistrik, M., Marhold, J., et al. (2011). Cep63 recruits Cdk1 to the centrosome: implications for regulation of mitotic entry, centrosome amplification, and genome maintenance. Cancer Research, 71(6), 2129–2139. https://doi.org/10.1158/0008-5472.CAN-10-2684.

    Article  CAS  PubMed  Google Scholar 

  22. Stearns, T., Evans, L., & Kirschner, M. (1991). Gamma-tubulin is a highly conserved component of the centrosome. Cell, 65(5), 825–836. https://doi.org/10.1016/0092-8674(91)90390-k.

    Article  CAS  PubMed  Google Scholar 

  23. Strnad, P., Leidel, S., Vinogradova, T., Euteneuer, U., Khodjakov, A., & Gonczy, P. (2007). Regulated HsSAS-6 levels ensure formation of a single procentriole per centriole during the centrosome duplication cycle. Developmental Cell, 13(2), 203–213. https://doi.org/10.1016/j.devcel.2007.07.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. D’Assoro, A. B., Lingle, W. L., & Salisbury, J. L. (2002). Centrosome amplification and the development of cancer. Oncogene, 21(40), 6146–6153. https://doi.org/10.1038/sj.onc.1205772.

    Article  CAS  PubMed  Google Scholar 

  25. Marteil, G., Guerrero, A., Vieira, A. F., de Almeida, B. P., Machado, P., Mendonca, S., et al. (2018). Over-elongation of centrioles in cancer promotes centriole amplification and chromosome missegregation. Nature Communications, 9(1), 1258. https://doi.org/10.1038/s41467-018-03641-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Nigg, E. A. (2006). Origins and consequences of centrosome aberrations in human cancers. International Journal of Cancer, 119(12), 2717–2723. https://doi.org/10.1002/ijc.22245.

    Article  CAS  PubMed  Google Scholar 

  27. Chan, J. Y. (2011). A clinical overview of centrosome amplification in human cancers. International Journal of Biological Sciences, 7(8), 1122–1144. https://doi.org/10.7150/ijbs.7.1122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Lingle, W. L., Barrett, S. L., Negron, V. C., D’Assoro, A. B., Boeneman, K., Liu, W., et al. (2002). Centrosome amplification drives chromosomal instability in breast tumor development. Proceedings of the National Academy of Sciences of the United States of America, 99(4), 1978–1983. https://doi.org/10.1073/pnas.032479999.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Mittal, K., Ogden, A., Reid, M. D., Rida, P. C., Varambally, S., & Aneja, R. (2015). Amplified centrosomes may underlie aggressive disease course in pancreatic ductal adenocarcinoma. Cell Cycle, 14(17), 2798–2809. https://doi.org/10.1080/15384101.2015.1068478.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Pannu, V., Mittal, K., Cantuaria, G., Reid, M. D., Li, X., Donthamsetty, S., et al. (2015). Rampant centrosome amplification underlies more aggressive disease course of triple negative breast cancers. Oncotarget, 6(12), 10487–10497. https://doi.org/10.18632/oncotarget.3402.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Duelli, D. M., Hearn, S., Myers, M. P., & Lazebnik, Y. (2005). A primate virus generates transformed human cells by fusion. The Journal of Cell Biology, 171(3), 493–503. https://doi.org/10.1083/jcb.200507069.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Khodjakov, A., Rieder, C. L., Sluder, G., Cassels, G., Sibon, O., & Wang, C. L. (2002). De novo formation of centrosomes in vertebrate cells arrested during S phase. The Journal of Cell Biology, 158(7), 1171–1181. https://doi.org/10.1083/jcb.200205102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. La Terra, S., English, C. N., Hergert, P., McEwen, B. F., Sluder, G., & Khodjakov, A. (2005). The de novo centriole assembly pathway in HeLa cells: cell cycle progression and centriole assembly/maturation. The Journal of Cell Biology, 168(5), 713–722. https://doi.org/10.1083/jcb.200411126.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Meraldi, P., Honda, R., & Nigg, E. A. (2002). Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53-/- cells. The EMBO Journal, 21(4), 483–492. https://doi.org/10.1093/emboj/21.4.483.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Shekhar, M. P., Lyakhovich, A., Visscher, D. W., Heng, H., & Kondrat, N. (2002). Rad6 overexpression induces multinucleation, centrosome amplification, abnormal mitosis, aneuploidy, and transformation. Cancer Research, 62(7), 2115–2124.

    CAS  PubMed  Google Scholar 

  36. Duensing, A., Liu, Y., Perdreau, S. A., Kleylein-Sohn, J., Nigg, E. A., & Duensing, S. (2007). Centriole overduplication through the concurrent formation of multiple daughter centrioles at single maternal templates. Oncogene, 26(43), 6280–6288. https://doi.org/10.1038/sj.onc.1210456.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Duensing, S., Lee, L. Y., Duensing, A., Basile, J., Piboonniyom, S., Gonzalez, S., et al. (2000). The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle. Proceedings of the National Academy of Sciences of the United States of America, 97(18), 10002–10007. https://doi.org/10.1073/pnas.170093297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Borel, F., Lohez, O. D., Lacroix, F. B., & Margolis, R. L. (2002). Multiple centrosomes arise from tetraploidy checkpoint failure and mitotic centrosome clusters in p53 and RB pocket protein-compromised cells. Proceedings of the National Academy of Sciences of the United States of America, 99(15), 9819–9824. https://doi.org/10.1073/pnas.152205299.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Karakaya, K., Herbst, F., Ball, C., Glimm, H., Kramer, A., & Loffler, H. (2012). Overexpression of EVI1 interferes with cytokinesis and leads to accumulation of cells with supernumerary centrosomes in G0/1 phase. Cell Cycle, 11(18), 3492–3503. https://doi.org/10.4161/cc.21801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Anand, S., Penrhyn-Lowe, S., & Venkitaraman, A. R. (2003). AURORA-A amplification overrides the mitotic spindle assembly checkpoint, inducing resistance to Taxol. Cancer Cell, 3(1), 51–62. https://doi.org/10.1016/s1535-6108(02)00235-0.

    Article  CAS  PubMed  Google Scholar 

  41. Difilippantonio, M. J., Ghadimi, B. M., Howard, T., Camps, J., Nguyen, Q. T., Ferris, D. K., et al. (2009). Nucleation capacity and presence of centrioles define a distinct category of centrosome abnormalities that induces multipolar mitoses in cancer cells. Environmental and Molecular Mutagenesis, 50(8), 672–696. https://doi.org/10.1002/em.20532.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Hut, H. M., Lemstra, W., Blaauw, E. H., Van Cappellen, G. W., Kampinga, H. H., & Sibon, O. C. (2003). Centrosomes split in the presence of impaired DNA integrity during mitosis. Molecular Biology of the Cell, 14(5), 1993–2004. https://doi.org/10.1091/mbc.e02-08-0510.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Levis, A. G., & Marin, G. (1963). Induction of multipolar spindles by X-radiation in mammalian cells in vitro. Experimental Cell Research, 31, 448–451. https://doi.org/10.1016/0014-4827(63)90026-0.

    Article  CAS  PubMed  Google Scholar 

  44. Loffler, H., Fechter, A., Liu, F. Y., Poppelreuther, S., & Kramer, A. (2013). DNA damage-induced centrosome amplification occurs via excessive formation of centriolar satellites. Oncogene, 32(24), 2963–2972. https://doi.org/10.1038/onc.2012.310.

    Article  CAS  PubMed  Google Scholar 

  45. Mikule, K., Delaval, B., Kaldis, P., Jurcyzk, A., Hergert, P., & Doxsey, S. (2007). Loss of centrosome integrity induces p38-p53-p21-dependent G1-S arrest. Nature Cell Biology, 9(2), 160–170. https://doi.org/10.1038/ncb1529.

    Article  CAS  PubMed  Google Scholar 

  46. Sato, C., Kuriyama, R., & Nishizawa, K. (1983). Microtubule-organizing centers abnormal in number, structure, and nucleating activity in x-irradiated mammalian cells. The Journal of Cell Biology, 96(3), 776–782. https://doi.org/10.1083/jcb.96.3.776.

    Article  CAS  PubMed  Google Scholar 

  47. D’Assoro, A. B., Barrett, S. L., Folk, C., Negron, V. C., Boeneman, K., Busby, R., et al. (2002). Amplified centrosomes in breast cancer: a potential indicator of tumor aggressiveness. Breast Cancer Research and Treatment, 75(1), 25–34. https://doi.org/10.1023/a:1016550619925.

    Article  PubMed  Google Scholar 

  48. Mittal, K., Choi, D. H., Ogden, A., Donthamsetty, S., Melton, B. D., Gupta, M. V., et al. (2017). Amplified centrosomes and mitotic index display poor concordance between patient tumors and cultured cancer cells. Scientific Reports, 7, 43984. https://doi.org/10.1038/srep43984.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Ogden, A., Rida, P. C. G., & Aneja, R. (2017). Centrosome amplification: a suspect in breast cancer and racial disparities. Endocrine-Related Cancer, 24(9), T47–T64. https://doi.org/10.1530/ERC-17-0072.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Loncarek, J., Hergert, P., Magidson, V., & Khodjakov, A. (2008). Control of daughter centriole formation by the pericentriolar material. Nature Cell Biology, 10(3), 322–328. https://doi.org/10.1038/ncb1694.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Starita, L. M., Machida, Y., Sankaran, S., Elias, J. E., Griffin, K., Schlegel, B. P., et al. (2004). BRCA1-dependent ubiquitination of gamma-tubulin regulates centrosome number. Molecular and Cellular Biology, 24(19), 8457–8466. https://doi.org/10.1128/MCB.24.19.8457-8466.2004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Bornens, M. (2002). Centrosome composition and microtubule anchoring mechanisms. Current Opinion in Cell Biology, 14(1), 25–34. https://doi.org/10.1016/s0955-0674(01)00290-3.

    Article  CAS  PubMed  Google Scholar 

  53. Sonnen, K. F., Schermelleh, L., Leonhardt, H., & Nigg, E. A. (2012). 3D-structured illumination microscopy provides novel insight into architecture of human centrosomes. Biology Open, 1(10), 965–976. https://doi.org/10.1242/bio.20122337.

  54. Vorobjev, I. A., & Chentsov, Y. S. (1980). The ultrastructure of centriole in mammalian tissue culture cells. Cell Biology International Reports, 4(11), 1037–1044. https://doi.org/10.1016/0309-1651(80)90177-0.

    Article  CAS  PubMed  Google Scholar 

  55. Schmidt, T. I., Kleylein-Sohn, J., Westendorf, J., Le Clech, M., Lavoie, S. B., Stierhof, Y. D., et al. (2009). Control of centriole length by CPAP and CP110. Current Biology, 19(12), 1005–1011. https://doi.org/10.1016/j.cub.2009.05.016.

    Article  CAS  PubMed  Google Scholar 

  56. Tang, C. J., Fu, R. H., Wu, K. S., Hsu, W. B., & Tang, T. K. (2009). CPAP is a cell-cycle regulated protein that controls centriole length. Nature Cell Biology, 11(7), 825–831. https://doi.org/10.1038/ncb1889.

    Article  CAS  PubMed  Google Scholar 

  57. Zheng, X., Ramani, A., Soni, K., Gottardo, M., Zheng, S., Ming Gooi, L., et al. (2016). Molecular basis for CPAP-tubulin interaction in controlling centriolar and ciliary length. Nature Communications, 7, 11874. https://doi.org/10.1038/ncomms11874.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Mittal, K., & Aneja, R. (2020). Spotlighting the hypoxia-centrosome amplification axis. Medicinal Research Reviews. https://doi.org/10.1002/med.21663.

  59. Bagheri-Yarmand, R., Biernacka, A., Hunt, K. K., & Keyomarsi, K. (2010). Low molecular weight cyclin E overexpression shortens mitosis, leading to chromosome missegregation and centrosome amplification. Cancer Research, 70(12), 5074–5084. https://doi.org/10.1158/0008-5472.CAN-09-4094.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Loh, J. K., Lieu, A. S., Chou, C. H., Lin, F. Y., Wu, C. H., Howng, S. L., et al. (2010). Differential expression of centrosomal proteins at different stages of human glioma. BMC Cancer, 10, 268. https://doi.org/10.1186/1471-2407-10-268.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Reiter, R., Gais, P., Jutting, U., Steuer-Vogt, M. K., Pickhard, A., Bink, K., et al. (2006). Aurora kinase A messenger RNA overexpression is correlated with tumor progression and shortened survival in head and neck squamous cell carcinoma. Clinical Cancer Research, 12(17), 5136–5141. https://doi.org/10.1158/1078-0432.CCR-05-1650.

    Article  CAS  PubMed  Google Scholar 

  62. Reiter, R., Gais, P., Steuer-Vogt, M. K., Boulesteix, A. L., Deutschle, T., Hampel, R., et al. (2009). Centrosome abnormalities in head and neck squamous cell carcinoma (HNSCC). Acta Oto-Laryngologica, 129(2), 205–213. https://doi.org/10.1080/00016480802165767.

    Article  CAS  PubMed  Google Scholar 

  63. Yamamoto, Y., Matsuyama, H., Furuya, T., Oga, A., Yoshihiro, S., Okuda, M., et al. (2004). Centrosome hyperamplification predicts progression and tumor recurrence in bladder cancer. Clinical Cancer Research, 10(19), 6449–6455. https://doi.org/10.1158/1078-0432.CCR-04-0773.

    Article  CAS  PubMed  Google Scholar 

  64. Ganem, N. J., Godinho, S. A., & Pellman, D. (2009). A mechanism linking extra centrosomes to chromosomal instability. Nature, 460(7252), 278–282. https://doi.org/10.1038/nature08136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Anderhub, S. J., Kramer, A., & Maier, B. (2012). Centrosome amplification in tumorigenesis. Cancer Letters, 322(1), 8–17. https://doi.org/10.1016/j.canlet.2012.02.006.

    Article  CAS  PubMed  Google Scholar 

  66. Godinho, S. A., Kwon, M., & Pellman, D. (2009). Centrosomes and cancer: how cancer cells divide with too many centrosomes. Cancer Metastasis Reviews, 28(1–2), 85–98. https://doi.org/10.1007/s10555-008-9163-6.

    Article  CAS  PubMed  Google Scholar 

  67. Milunovic-Jevtic, A., Mooney, P., Sulerud, T., Bisht, J., & Gatlin, J. C. (2016). Centrosomal clustering contributes to chromosomal instability and cancer. Current Opinion in Biotechnology, 40, 113–118. https://doi.org/10.1016/j.copbio.2016.03.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Ogden, A., Rida, P. C., & Aneja, R. (2012). Let’s huddle to prevent a muddle: centrosome declustering as an attractive anticancer strategy. Cell Death and Differentiation, 19(8), 1255–1267. https://doi.org/10.1038/cdd.2012.61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kleylein-Sohn, J., Pollinger, B., Ohmer, M., Hofmann, F., Nigg, E. A., Hemmings, B. A., et al. (2012). Acentrosomal spindle organization renders cancer cells dependent on the kinesin HSET. Journal of Cell Science, 125(Pt 22), 5391–5402, doi:https://doi.org/10.1242/jcs.107474.

  70. Kwon, M., Godinho, S. A., Chandhok, N. S., Ganem, N. J., Azioune, A., Thery, M., et al. (2008). Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes. Genes & Development, 22(16), 2189–2203. https://doi.org/10.1101/gad.1700908.

    Article  CAS  Google Scholar 

  71. Grinberg-Rashi, H., Ofek, E., Perelman, M., Skarda, J., Yaron, P., Hajduch, M., et al. (2009). The expression of three genes in primary non-small cell lung cancer is associated with metastatic spread to the brain. Clinical Cancer Research, 15(5), 1755–1761. https://doi.org/10.1158/1078-0432.CCR-08-2124.

    Article  CAS  PubMed  Google Scholar 

  72. Pannu, V., Rida, P. C., Ogden, A., Turaga, R. C., Donthamsetty, S., Bowen, N. J., et al. (2015). HSET overexpression fuels tumor progression via centrosome clustering-independent mechanisms in breast cancer patients. Oncotarget, 6(8), 6076–6091. https://doi.org/10.18632/oncotarget.3475.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Pawar, S., Donthamsetty, S., Pannu, V., Rida, P., Ogden, A., Bowen, N., et al. (2014). KIFCI, a novel putative prognostic biomarker for ovarian adenocarcinomas: delineating protein interaction networks and signaling circuitries. J Ovarian Res, 7, 53. https://doi.org/10.1186/1757-2215-7-53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Rath, O., & Kozielski, F. (2012). Kinesins and cancer. Nature Reviews. Cancer, 12(8), 527–539. https://doi.org/10.1038/nrc3310.

    Article  CAS  PubMed  Google Scholar 

  75. De, S., Cipriano, R., Jackson, M. W., & Stark, G. R. (2009). Overexpression of kinesins mediates docetaxel resistance in breast cancer cells. Cancer Research, 69(20), 8035–8042. https://doi.org/10.1158/0008-5472.CAN-09-1224.

    Article  CAS  PubMed  Google Scholar 

  76. Sekino, Y., Oue, N., Shigematsu, Y., Ishikawa, A., Sakamoto, N., Sentani, K., et al. (2017). KIFC1 induces resistance to docetaxel and is associated with survival of patients with prostate cancer. Urologic Oncology, 35(1), 31 e13–31 e20, doi:https://doi.org/10.1016/j.urolonc.2016.08.007.

  77. Sekino, Y., Oue, N., Koike, Y., Shigematsu, Y., Sakamoto, N., Sentani, K., et al. (2019). KIFC1 inhibitor CW069 induces apoptosis and reverses resistance to docetaxel in prostate cancer. Journal of Clinical Medicine, 8(2). https://doi.org/10.3390/jcm8020225.

  78. Ogden, A., Rida, P. C., & Aneja, R. (2013). Heading off with the herd: how cancer cells might maneuver supernumerary centrosomes for directional migration. Cancer Metastasis Reviews, 32(1–2), 269–287. https://doi.org/10.1007/s10555-012-9413-5.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Koutsami, M. K., Tsantoulis, P. K., Kouloukoussa, M., Apostolopoulou, K., Pateras, I. S., Spartinou, Z., et al. (2006). Centrosome abnormalities are frequently observed in non-small-cell lung cancer and are associated with aneuploidy and cyclin E overexpression. The Journal of Pathology, 209(4), 512–521. https://doi.org/10.1002/path.2005.

    Article  CAS  PubMed  Google Scholar 

  80. Jung, C. K., Jung, J. H., Lee, K. Y., Kang, C. S., Kim, M., Ko, Y. H., et al. (2007). Centrosome abnormalities in non-small cell lung cancer: correlations with DNA aneuploidy and expression of cell cycle regulatory proteins. Pathology, Research and Practice, 203(12), 839–847. https://doi.org/10.1016/j.prp.2007.08.004.

    Article  CAS  PubMed  Google Scholar 

  81. Gisselsson, D., Jonson, T., Yu, C., Martins, C., Mandahl, N., Wiegant, J., et al. (2002). Centrosomal abnormalities, multipolar mitoses, and chromosomal instability in head and neck tumours with dysfunctional telomeres. British Journal of Cancer, 87(2), 202–207. https://doi.org/10.1038/sj.bjc.6600438.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Gong, Y., Sun, Y., McNutt, M. A., Sun, Q., Hou, L., Liu, H., et al. (2009). Localization of TEIF in the centrosome and its functional association with centrosome amplification in DNA damage, telomere dysfunction and human cancers. Oncogene, 28(12), 1549–1560. https://doi.org/10.1038/onc.2008.503.

    Article  CAS  PubMed  Google Scholar 

  83. Gisselsson, D., Gorunova, L., Hoglund, M., Mandahl, N., & Elfving, P. (2004). Telomere shortening and mitotic dysfunction generate cytogenetic heterogeneity in a subgroup of renal cell carcinomas. British Journal of Cancer, 91(2), 327–332. https://doi.org/10.1038/sj.bjc.6601803.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Gisselsson, D., Palsson, E., Yu, C., Mertens, F., & Mandahl, N. (2004). Mitotic instability associated with late genomic changes in bone and soft tissue tumours. Cancer Letters, 206(1), 69–76. https://doi.org/10.1016/j.canlet.2003.10.022.

    Article  CAS  PubMed  Google Scholar 

  85. Ghadimi, B. M., Sackett, D. L., Difilippantonio, M. J., Schrock, E., Neumann, T., Jauho, A., et al. (2000). Centrosome amplification and instability occurs exclusively in aneuploid, but not in diploid colorectal cancer cell lines, and correlates with numerical chromosomal aberrations. Genes, Chromosomes & Cancer, 27(2), 183–190.

    Article  CAS  Google Scholar 

  86. Kawamura, K., Izumi, H., Ma, Z., Ikeda, R., Moriyama, M., Tanaka, T., et al. (2004). Induction of centrosome amplification and chromosome instability in human bladder cancer cells by p53 mutation and cyclin E overexpression. Cancer Research, 64(14), 4800–4809. https://doi.org/10.1158/0008-5472.CAN-03-3908.

    Article  CAS  PubMed  Google Scholar 

  87. Jiang, F., Caraway, N. P., Sabichi, A. L., Zhang, H. Z., Ruitrok, A., Grossman, H. B., et al. (2003). Centrosomal abnormality is common in and a potential biomarker for bladder cancer. International Journal of Cancer, 106(5), 661–665. https://doi.org/10.1002/ijc.11251.

    Article  CAS  PubMed  Google Scholar 

  88. Yamamoto, Y., Matsuyama, H., Kawauchi, S., Furuya, T., Liu, X. P., Ikemoto, K., et al. (2006). Biological characteristics in bladder cancer depend on the type of genetic instability. Clinical Cancer Research, 12(9), 2752–2758. https://doi.org/10.1158/1078-0432.CCR-05-0805.

    Article  CAS  PubMed  Google Scholar 

  89. Godinho, S. A., Picone, R., Burute, M., Dagher, R., Su, Y., Leung, C. T., et al. (2014). Oncogene-like induction of cellular invasion from centrosome amplification. Nature, 510(7503), 167–171. https://doi.org/10.1038/nature13277.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Basto, R., Brunk, K., Vinadogrova, T., Peel, N., Franz, A., Khodjakov, A., et al. (2008). Centrosome amplification can initiate tumorigenesis in flies. Cell, 133(6), 1032–1042. https://doi.org/10.1016/j.cell.2008.05.039.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Pihan, G. A., Wallace, J., Zhou, Y., & Doxsey, S. J. (2003). Centrosome abnormalities and chromosome instability occur together in pre-invasive carcinomas. Cancer Research, 63(6), 1398–1404.

    CAS  PubMed  Google Scholar 

  92. Kayser, G., Gerlach, U., Walch, A., Nitschke, R., Haxelmans, S., Kayser, K., et al. (2005). Numerical and structural centrosome aberrations are an early and stable event in the adenoma-carcinoma sequence of colorectal carcinomas. Virchows Archiv, 447(1), 61–65. https://doi.org/10.1007/s00428-004-1191-1.

    Article  CAS  PubMed  Google Scholar 

  93. Hsu, L. C., Kapali, M., DeLoia, J. A., & Gallion, H. H. (2005). Centrosome abnormalities in ovarian cancer. International Journal of Cancer, 113(5), 746–751. https://doi.org/10.1002/ijc.20633.

    Article  CAS  PubMed  Google Scholar 

  94. Chng, W. J., Ahmann, G. J., Henderson, K., Santana-Davila, R., Greipp, P. R., Gertz, M. A., et al. (2006). Clinical implication of centrosome amplification in plasma cell neoplasm. Blood, 107(9), 3669–3675. https://doi.org/10.1182/blood-2005-09-3810.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Kronenwett, U., Huwendiek, S., Castro, J., Ried, T., & Auer, G. (2005). Characterisation of breast fine-needle aspiration biopsies by centrosome aberrations and genomic instability. British Journal of Cancer, 92(2), 389–395. https://doi.org/10.1038/sj.bjc.6602246.

    Article  CAS  PubMed  Google Scholar 

  96. Kuhn, E., Wang, T. L., Doberstein, K., Bahadirli-Talbott, A., Ayhan, A., Sehdev, A. S., et al. (2016). CCNE1 amplification and centrosome number abnormality in serous tubal intraepithelial carcinoma: further evidence supporting its role as a precursor of ovarian high-grade serous carcinoma. Modern Pathology, 29(10), 1254–1261. https://doi.org/10.1038/modpathol.2016.101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Kuo, K. K., Sato, N., Mizumoto, K., Maehara, N., Yonemasu, H., Ker, C. G., et al. (2000). Centrosome abnormalities in human carcinomas of the gallbladder and intrahepatic and extrahepatic bile ducts. Hepatology, 31(1), 59–64. https://doi.org/10.1002/hep.510310112.

    Article  CAS  PubMed  Google Scholar 

  98. Skyldberg, B., Fujioka, K., Hellstrom, A. C., Sylven, L., Moberger, B., & Auer, G. (2001). Human papillomavirus infection, centrosome aberration, and genetic stability in cervical lesions. Modern Pathology, 14(4), 279–284. https://doi.org/10.1038/modpathol.3880303.

    Article  CAS  PubMed  Google Scholar 

  99. Toma, M. I., Friedrich, K., Meyer, W., Frohner, M., Schneider, S., Wirth, M., et al. (2010). Correlation of centrosomal aberrations with cell differentiation and DNA ploidy in prostate cancer. Analytical and Quantitative Cytology and Histology, 32(1), 1–10.

    PubMed  Google Scholar 

  100. Katsetos, C. D., Reddy, G., Draberova, E., Smejkalova, B., Del Valle, L., Ashraf, Q., et al. (2006). Altered cellular distribution and subcellular sorting of gamma-tubulin in diffuse astrocytic gliomas and human glioblastoma cell lines. Journal of Neuropathology and Experimental Neurology, 65(5), 465–477. https://doi.org/10.1097/01.jnen.0000229235.20995.6e.

    Article  CAS  PubMed  Google Scholar 

  101. Cai, Y., Li, B. Q., & Cheng, Q. M. (2004). Centrosome hyperamplificationin oral precancerous lesions and squamous cell carcinomas. Hua Xi Kou Qiang Yi Xue Za Zhi, 22(3), 238–241.

    PubMed  Google Scholar 

  102. Gustafson, L. M., Gleich, L. L., Fukasawa, K., Chadwell, J., Miller, M. A., Stambrook, P. J., et al. (2000). Centrosome hyperamplification in head and neck squamous cell carcinoma: a potential phenotypic marker of tumor aggressiveness. Laryngoscope, 110(11), 1798–1801. https://doi.org/10.1097/00005537-200011000-00004.

    Article  CAS  PubMed  Google Scholar 

  103. Moskovszky, L., Dezso, K., Athanasou, N., Szendroi, M., Kopper, L., Kliskey, K., et al. (2010). Centrosome abnormalities in giant cell tumour of bone: possible association with chromosomal instability. Modern Pathology, 23(3), 359–366. https://doi.org/10.1038/modpathol.2009.134.

    Article  PubMed  Google Scholar 

  104. Pinheiro, C. A., Soares, I. C., Penna, V., Squire, J., Reis, R. M. V., da Silva, S. R. M., et al. (2017). Centrosome amplification in chondrosarcomas: a primary cell culture and cryopreserved tumor sample study. Oncology Letters, 13(3), 1835. https://doi.org/10.3892/ol.2017.5633.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Kramer, A., Neben, K., & Ho, A. D. (2005). Centrosome aberrations in hematological malignancies. Cell Biology International, 29(5), 375–383. https://doi.org/10.1016/j.cellbi.2005.03.004.

    Article  CAS  PubMed  Google Scholar 

  106. Kramer, A., Schweizer, S., Neben, K., Giesecke, C., Kalla, J., Katzenberger, T., et al. (2003). Centrosome aberrations as a possible mechanism for chromosomal instability in non-Hodgkin’s lymphoma. Leukemia, 17(11), 2207–2213. https://doi.org/10.1038/sj.leu.2403142.

    Article  CAS  PubMed  Google Scholar 

  107. Hensel, M., Zoz, M., Giesecke, C., Benner, A., Neben, K., Jauch, A., et al. (2007). High rate of centrosome aberrations and correlation with proliferative activity in patients with untreated B-cell chronic lymphocytic leukemia. International Journal of Cancer, 121(5), 978–983. https://doi.org/10.1002/ijc.22752.

    Article  CAS  PubMed  Google Scholar 

  108. Neben, K., Ott, G., Schweizer, S., Kalla, J., Tews, B., Katzenberger, T., et al. (2007). Expression of centrosome-associated gene products is linked to tetraploidization in mantle cell lymphoma. International Journal of Cancer, 120(8), 1669–1677. https://doi.org/10.1002/ijc.22404.

    Article  CAS  PubMed  Google Scholar 

  109. Neben, K., Giesecke, C., Schweizer, S., Ho, A. D., & Kramer, A. (2003). Centrosome aberrations in acute myeloid leukemia are correlated with cytogenetic risk profile. Blood, 101(1), 289–291. https://doi.org/10.1182/blood-2002-04-1188.

    Article  CAS  PubMed  Google Scholar 

  110. Mittal, K., Toss, M. S., Wei, G., Kaur, J., Choi, D. H., Melton, B. D., et al. (2020). A quantitative centrosomal amplification score predicts local recurrence in ductal carcinoma in situ. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.CCR-19-1272.

  111. Mittal, K., Kaur, J., Wei, G., Toss, M., Osan, R. M., Janssen, E., et al. (2019). Abstract P5-18-02: a quantitative centrosomal amplification score (CAS) predicts local recurrence in ductal carcinoma. In Situ, 79.

  112. Wang, M., Knudsen, B. S., Nagle, R. B., Rogers, G. C., & Cress, A. E. (2019). A method of quantifying centrosomes at the single-cell level in human normal and cancer tissue. Molecular Biology of the Cell, 30(7), 811–819. https://doi.org/10.1091/mbc.E18-10-0651.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Sampson, J., O’Regan, L., Dyer, M. J. S., Bayliss, R., & Fry, A. M. (2017). Hsp72 and Nek6 cooperate to cluster amplified centrosomes in cancer cells. Cancer Research, 77(18), 4785–4796. https://doi.org/10.1158/0008-5472.CAN-16-3233.

    Article  CAS  PubMed  Google Scholar 

  114. D’Assoro, A. B., Busby, R., Acu, I. D., Quatraro, C., Reinholz, M. M., Farrugia, D. J., et al. (2008). Impaired p53 function leads to centrosome amplification, acquired ERalpha phenotypic heterogeneity and distant metastases in breast cancer MCF-7 xenografts. Oncogene, 27(28), 3901–3911. https://doi.org/10.1038/onc.2008.18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Ganapathi Sankaran, D., Stemm-Wolf, A. J., & Pearson, C. G. (2019). CEP135 isoform dysregulation promotes centrosome amplification in breast cancer cells. Molecular Biology of the Cell, 30(10), 1230–1244. https://doi.org/10.1091/mbc.E18-10-0674.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Li, X., Song, N., Liu, L., Liu, X., Ding, X., Song, X., et al. (2017). USP9X regulates centrosome duplication and promotes breast carcinogenesis. Nature Communications, 8, 14866. https://doi.org/10.1038/ncomms14866.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Yoshino, Y., Qi, H., Fujita, H., Shirota, M., Abe, S., Komiyama, Y., et al. (2018). BRCA1-interacting protein OLA1 requires interaction with BARD1 to regulate centrosome number. Molecular Cancer Research, 16(10), 1499–1511. https://doi.org/10.1158/1541-7786.MCR-18-0269.

    Article  CAS  PubMed  Google Scholar 

  118. Arnandis, T., Monteiro, P., Adams, S. D., Bridgeman, V. L., Rajeeve, V., Gadaleta, E., et al. (2018). Oxidative stress in cells with extra centrosomes drives non-cell-autonomous invasion. Developmental Cell, 47(4), 409–424 e409. https://doi.org/10.1016/j.devcel.2018.10.026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Korzeniewski, N., Wheeler, S., Chatterjee, P., Duensing, A., & Duensing, S. (2010). A novel role of the aryl hydrocarbon receptor (AhR) in centrosome amplification - implications for chemoprevention. Molecular Cancer, 9, 153. https://doi.org/10.1186/1476-4598-9-153.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Mariappan, A., Soni, K., Schorpp, K., Zhao, F., Minakar, A., Zheng, X., et al. (2019). Inhibition of CPAP-tubulin interaction prevents proliferation of centrosome-amplified cancer cells. The EMBO Journal, 38(2). https://doi.org/10.15252/embj.201899876.

  121. Harrison Pitner, M. K., & Saavedra, H. I. (2013). Cdk4 and nek2 signal binucleation and centrosome amplification in a her2+ breast cancer model. PLoS One, 8(6), e65971. https://doi.org/10.1371/journal.pone.0065971.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Leontovich, A. A., Salisbury, J. L., Veroux, M., Tallarita, T., Billadeau, D., McCubrey, J., et al. (2013). Inhibition of Cdk2 activity decreases Aurora-A kinase centrosomal localization and prevents centrosome amplification in breast cancer cells. Oncology Reports, 29(5), 1785–1788. https://doi.org/10.3892/or.2013.2313.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Yoshino, Y., Qi, H., Kanazawa, R., Sugamata, M., Suzuki, K., Kobayashi, A., et al. (2019). RACK1 regulates centriole duplication by controlling localization of BRCA1 to the centrosome in mammary tissue-derived cells. Oncogene, 38(16), 3077–3092. https://doi.org/10.1038/s41388-018-0647-8.

    Article  CAS  PubMed  Google Scholar 

  124. Osman, M. A., Antonisamy, W. J., & Yakirevich, E. (2020). IQGAP1 control of centrosome function defines distinct variants of triple negative breast cancer. Oncotarget, 11(26), 2493–2511. https://doi.org/10.18632/oncotarget.27623.

    Article  PubMed  PubMed Central  Google Scholar 

  125. Denu, R. A., Shabbir, M., Nihal, M., Singh, C. K., Longley, B. J., Burkard, M. E., et al. (2018). Centriole overduplication is the predominant mechanism leading to centrosome amplification in melanoma. Molecular Cancer Research, 16(3), 517–527. https://doi.org/10.1158/1541-7786.MCR-17-0197.

    Article  CAS  PubMed  Google Scholar 

  126. Landen Jr., C. N., Lin, Y. G., Immaneni, A., Deavers, M. T., Merritt, W. M., Spannuth, W. A., et al. (2007). Overexpression of the centrosomal protein Aurora-A kinase is associated with poor prognosis in epithelial ovarian cancer patients. Clinical Cancer Research, 13(14), 4098–4104. https://doi.org/10.1158/1078-0432.CCR-07-0431.

    Article  CAS  PubMed  Google Scholar 

  127. Mittal, K., Choi, D. H., Klimov, S., Pawar, S., Kaur, R., Mitra, A. K., et al. (2016). A centrosome clustering protein, KIFC1, predicts aggressive disease course in serous ovarian adenocarcinomas. Journal of Ovarian Research, 9, 17. https://doi.org/10.1186/s13048-016-0224-0.

  128. Zhang, Y., Tian, Y., Yu, J. J., He, J., Luo, J., Zhang, S., et al. (2013). Overexpression of WDR62 is associated with centrosome amplification in human ovarian cancer. J Ovarian Res, 6(1), 55. https://doi.org/10.1186/1757-2215-6-55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Bijnsdorp, I. V., Hodzic, J., Lagerweij, T., Westerman, B., Krijgsman, O., Broeke, J., et al. (2016). miR-129-3p controls centrosome number in metastatic prostate cancer cells by repressing CP110. Oncotarget, 7(13), 16676–16687. https://doi.org/10.18632/oncotarget.7572.

    Article  PubMed  PubMed Central  Google Scholar 

  130. Li, J., Xuan, J. W., Khatamianfar, V., Valiyeva, F., Moussa, M., Sadek, A., et al. (2014). SKA1 over-expression promotes centriole over-duplication, centrosome amplification and prostate tumourigenesis. The Journal of Pathology, 234(2), 178–189. https://doi.org/10.1002/path.4374.

    Article  CAS  PubMed  Google Scholar 

  131. Pihan, G. A., Purohit, A., Wallace, J., Malhotra, R., Liotta, L., & Doxsey, S. J. (2001). Centrosome defects can account for cellular and genetic changes that characterize prostate cancer progression. Cancer Research, 61(5), 2212–2219.

    CAS  PubMed  Google Scholar 

  132. Takayasu, T., Hama, S., Yamasaki, F., Saito, T., Watanabe, Y., Nosaka, R., et al. (2015). p16 gene transfer induces centrosome amplification and abnormal nucleation associated with survivin downregulation in glioma cells. Pathobiology, 82(1), 1–8. https://doi.org/10.1159/000368196.

    Article  CAS  PubMed  Google Scholar 

  133. Duensing, S., Duensing, A., Crum, C. P., & Munger, K. (2001). Human papillomavirus type 16 E7 oncoprotein-induced abnormal centrosome synthesis is an early event in the evolving malignant phenotype. Cancer Research, 61(6), 2356–2360.

    CAS  PubMed  Google Scholar 

  134. Duensing, S., Duensing, A., Flores, E. R., Do, A., Lambert, P. F., & Munger, K. (2001). Centrosome abnormalities and genomic instability by episomal expression of human papillomavirus type 16 in raft cultures of human keratinocytes. Journal of Virology, 75(16), 7712–7716. https://doi.org/10.1128/JVI.75.16.7712-7716.2001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Grieshaber, S. S., Grieshaber, N. A., Miller, N., & Hackstadt, T. (2006). Chlamydia trachomatis causes centrosomal defects resulting in chromosomal segregation abnormalities. Traffic, 7(8), 940–949. https://doi.org/10.1111/j.1600-0854.2006.00439.x.

    Article  CAS  PubMed  Google Scholar 

  136. Duensing, A., Liu, Y., Spardy, N., Bartoli, K., Tseng, M., Kwon, J. A., et al. (2007). RNA polymerase II transcription is required for human papillomavirus type 16 E7- and hydroxyurea-induced centriole overduplication. Oncogene, 26(2), 215–223. https://doi.org/10.1038/sj.onc.1209782.

    Article  CAS  PubMed  Google Scholar 

  137. Shinmura, K., Kato, H., Kawanishi, Y., Igarashi, H., Inoue, Y., Yoshimura, K., et al. (2017). WDR62 overexpression is associated with a poor prognosis in patients with lung adenocarcinoma. Molecular Carcinogenesis, 56(8), 1984–1991. https://doi.org/10.1002/mc.22647.

    Article  CAS  PubMed  Google Scholar 

  138. Li, J. A., Liu, B. C., Song, Y., & Chen, X. (2018). Cyclin A2 regulates symmetrical mitotic spindle formation and centrosome amplification in human colon cancer cells. American Journal of Translational Research, 10(8), 2669–2676.

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Yoon, H. S., Ghaleb, A. M., Nandan, M. O., Hisamuddin, I. M., Dalton, W. B., & Yang, V. W. (2005). Kruppel-like factor 4 prevents centrosome amplification following gamma-irradiation-induced DNA damage. Oncogene, 24(25), 4017–4025. https://doi.org/10.1038/sj.onc.1208576.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Bahmanyar, S., Guiney, E. L., Hatch, E. M., Nelson, W. J., & Barth, A. I. (2010). Formation of extra centrosomal structures is dependent on beta-catenin. Journal of Cell Science, 123(Pt 18), 3125–3135, doi:https://doi.org/10.1242/jcs.064782.

  141. Mittal, K., Choi, D. H., Wei, G., Kaur, J., Klimov, S., Arora, K., et al. (2020). Hypoxia-induced centrosome amplification underlies aggressive disease course in HPV-negative oropharyngeal squamous cell carcinomas. Cancers (Basel), 12(2). https://doi.org/10.3390/cancers12020517.

  142. Fan, G., Sun, L., Shan, P., Zhang, X., Huan, J., Zhang, X., et al. (2015). Loss of KLF14 triggers centrosome amplification and tumorigenesis. Nature Communications, 6, 8450. https://doi.org/10.1038/ncomms9450.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Carroll, P. E., Okuda, M., Horn, H. F., Biddinger, P., Stambrook, P. J., Gleich, L. L., et al. (1999). Centrosome hyperamplification in human cancer: chromosome instability induced by p53 mutation and/or Mdm2 overexpression. Oncogene, 18(11), 1935–1944. https://doi.org/10.1038/sj.onc.1202515.

    Article  CAS  PubMed  Google Scholar 

  144. Berenjeno, I. M., Pineiro, R., Castillo, S. D., Pearce, W., McGranahan, N., Dewhurst, S. M., et al. (2017). Oncogenic PIK3CA induces centrosome amplification and tolerance to genome doubling. Nature Communications, 8(1), 1773. https://doi.org/10.1038/s41467-017-02002-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Denu, R. A., Sass, M. M., Johnson, J. M., Potts, G. K., Choudhary, A., Coon, J. J., et al. (2019). Polo-like kinase 4 maintains centriolar satellite integrity by phosphorylation of centrosomal protein 131 (CEP131). The Journal of Biological Chemistry, 294(16), 6531–6549. https://doi.org/10.1074/jbc.RA118.004867.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Mukhopadhyay, A., Sehgal, L., Bose, A., Gulvady, A., Senapati, P., Thorat, R., et al. (2016). 14-3-3gamma prevents centrosome amplification and neoplastic progression. Scientific Reports, 6, 26580. https://doi.org/10.1038/srep26580.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Jung, J. K., Jang, S. W., & Kim, J. M. (2016). A novel role for the deubiquitinase USP1 in the control of centrosome duplication. Cell Cycle, 15(4), 584–592. https://doi.org/10.1080/15384101.2016.1138185.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Adon, A. M., Zeng, X., Harrison, M. K., Sannem, S., Kiyokawa, H., Kaldis, P., et al. (2010). Cdk2 and Cdk4 regulate the centrosome cycle and are critical mediators of centrosome amplification in p53-null cells. Molecular and Cellular Biology, 30(3), 694–710. https://doi.org/10.1128/MCB.00253-09.

    Article  CAS  PubMed  Google Scholar 

  149. Coelho, P. A., Bury, L., Shahbazi, M. N., Liakath-Ali, K., Tate, P. H., Wormald, S., et al. (2015). Over-expression of Plk4 induces centrosome amplification, loss of primary cilia and associated tissue hyperplasia in the mouse. Open Biology, 5(12), 150209. https://doi.org/10.1098/rsob.150209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Chavali, P. L., Chandrasekaran, G., Barr, A. R., Tatrai, P., Taylor, C., Papachristou, E. K., et al. (2016). A CEP215-HSET complex links centrosomes with spindle poles and drives centrosome clustering in cancer. Nature Communications, 7, 11005. https://doi.org/10.1038/ncomms11005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Levine, M. S., Bakker, B., Boeckx, B., Moyett, J., Lu, J., Vitre, B., et al. (2017). Centrosome amplification is sufficient to promote spontaneous tumorigenesis in mammals. Developmental Cell, 40(3), 313–322 e315, doi:https://doi.org/10.1016/j.devcel.2016.12.022.

  152. Suzuki, J. I., Roy, B. C., Ogaeri, T., Kakinuma, N., & Kiyama, R. (2017). Depletion of tumor suppressor Kank1 induces centrosomal amplification via hyperactivation of RhoA. Experimental Cell Research, 353(2), 79–87. https://doi.org/10.1016/j.yexcr.2017.03.006.

    Article  CAS  PubMed  Google Scholar 

  153. Shumilov, A., Tsai, M. H., Schlosser, Y. T., Kratz, A. S., Bernhardt, K., Fink, S., et al. (2017). Epstein-Barr virus particles induce centrosome amplification and chromosomal instability. Nature Communications, 8, 14257. https://doi.org/10.1038/ncomms14257.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Werle, K., Chen, J., Xu, H. G., Zhao, R. X., He, Q., Lu, C., et al. (2014). Liver kinase B1 regulates the centrosome via PLK1. Cell Death & Disease, 5, –e1157. https://doi.org/10.1038/cddis.2014.135.

  155. Chen, T. Y., Syu, J. S., Lin, T. C., Cheng, H. L., Lu, F. L., & Wang, C. Y. (2015). Chloroquine alleviates etoposide-induced centrosome amplification by inhibiting CDK2 in adrenocortical tumor cells. Oncogenesis, 4, e180. https://doi.org/10.1038/oncsis.2015.37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Lopes, C. A. M., Mesquita, M., Cunha, A. I., Cardoso, J., Carapeta, S., Laranjeira, C., et al. (2018). Centrosome amplification arises before neoplasia and increases upon p53 loss in tumorigenesis. The Journal of Cell Biology, 217(7), 2353–2363. https://doi.org/10.1083/jcb.201711191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Suizu, F., Ryo, A., Wulf, G., Lim, J., & Lu, K. P. (2006). Pin1 regulates centrosome duplication, and its overexpression induces centrosome amplification, chromosome instability, and oncogenesis. Molecular and Cellular Biology, 26(4), 1463–1479. https://doi.org/10.1128/MCB.26.4.1463-1479.2006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Fournier, M., Orpinell, M., Grauffel, C., Scheer, E., Garnier, J. M., Ye, T., et al. (2016). KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in preventing centrosome amplification. Nature Communications, 7, 13227. https://doi.org/10.1038/ncomms13227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Shinmura, K., Kurabe, N., Goto, M., Yamada, H., Natsume, H., Konno, H., et al. (2014). PLK4 overexpression and its effect on centrosome regulation and chromosome stability in human gastric cancer. Molecular Biology Reports, 41(10), 6635–6644. https://doi.org/10.1007/s11033-014-3546-2.

    Article  CAS  PubMed  Google Scholar 

  160. Hanashiro, K., Kanai, M., Geng, Y., Sicinski, P., & Fukasawa, K. (2008). Roles of cyclins A and E in induction of centrosome amplification in p53-compromised cells. Oncogene, 27(40), 5288–5302. https://doi.org/10.1038/onc.2008.161.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Xu, Z., Shen, W., Pan, A., Sun, F., Zhang, J., Gao, P., et al. (2020). Decreased Nek9 expression correlates with aggressive behaviour and predicts unfavourable prognosis in breast cancer. Pathology, 52(3), 329–335. https://doi.org/10.1016/j.pathol.2019.11.008.

    Article  CAS  PubMed  Google Scholar 

  162. Schneeweiss, A., Sinn, H. P., Ehemann, V., Khbeis, T., Neben, K., Krause, U., et al. (2003). Centrosomal aberrations in primary invasive breast cancer are associated with nodal status and hormone receptor expression. International Journal of Cancer, 107(3), 346–352. https://doi.org/10.1002/ijc.11408.

    Article  CAS  PubMed  Google Scholar 

  163. Lingle, W. L., Lutz, W. H., Ingle, J. N., Maihle, N. J., & Salisbury, J. L. (1998). Centrosome hypertrophy in human breast tumors: implications for genomic stability and cell polarity. Proceedings of the National Academy of Sciences of the United States of America, 95(6), 2950–2955. https://doi.org/10.1073/pnas.95.6.2950.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Lingle, W. L., & Salisbury, J. L. (1999). Altered centrosome structure is associated with abnormal mitoses in human breast tumors. The American Journal of Pathology, 155(6), 1941–1951. https://doi.org/10.1016/S0002-9440(10)65513-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Yamamoto, Y., Matsuyama, H., Kawauchi, S., Matsumoto, H., Nagao, K., Ohmi, C., et al. (2006). Overexpression of polo-like kinase 1 (PLK1) and chromosomal instability in bladder cancer. Oncology, 70(3), 231–237. https://doi.org/10.1159/000094416.

    Article  PubMed  Google Scholar 

  166. Yamamoto, Y., Matsuyama, H., Chochi, Y., Okuda, M., Kawauchi, S., Inoue, R., et al. (2007). Overexpression of BUBR1 is associated with chromosomal instability in bladder cancer. Cancer Genetics and Cytogenetics, 174(1), 42–47. https://doi.org/10.1016/j.cancergencyto.2006.11.012.

    Article  CAS  PubMed  Google Scholar 

  167. Yamamoto, Y., Misumi, T., Eguchi, S., Chochi, Y., Kitahara, S., Nakao, M., et al. (2011). Centrosome amplification as a putative prognostic biomarker for the classification of urothelial carcinomas. Human Pathology, 42(12), 1923–1930. https://doi.org/10.1016/j.humpath.2011.02.013.

    Article  CAS  PubMed  Google Scholar 

  168. Miyachika, Y., Yamamoto, Y., Matsumoto, H., Nishijima, J., Kawai, Y., Nagao, K., et al. (2013). Centrosome amplification in bladder washing cytology specimens is a useful prognostic biomarker for non-muscle invasive bladder cancer. Cancer Genetics, 206(1–2), 12–18. https://doi.org/10.1016/j.cancergen.2012.11.004.

    Article  CAS  PubMed  Google Scholar 

  169. Roshani, L., Fujioka, K., Auer, G., Kjellman, M., Lagercrantz, S., & Larsson, C. (2002). Aberrations of centrosomes in adrenocortical tumors. International Journal of Oncology, 20(6), 1161–1165.

    PubMed  Google Scholar 

  170. Fukushi, D., Watanabe, N., Kasai, F., Haruta, M., Kikuchi, A., Kikuta, A., et al. (2009). Centrosome amplification is correlated with ploidy divergence, but not with MYCN amplification, in neuroblastoma tumors. Cancer Genetics and Cytogenetics, 188(1), 32–41. https://doi.org/10.1016/j.cancergencyto.2008.08.014.

    Article  CAS  PubMed  Google Scholar 

  171. Gao, Y., & Zhang, B. (2009). Expression of TEIF protein in colorectal tumors and its correlation with centrosome abnormality. Ai Zheng, 28(12), 1277–1282. https://doi.org/10.5732/cjc.009.10162.

    Article  CAS  PubMed  Google Scholar 

  172. Nakajima, T., Moriguchi, M., Mitsumoto, Y., Sekoguchi, S., Nishikawa, T., Takashima, H., et al. (2004). Centrosome aberration accompanied with p53 mutation can induce genetic instability in hepatocellular carcinoma. Modern Pathology, 17(6), 722–727. https://doi.org/10.1038/modpathol.3800115.

    Article  CAS  PubMed  Google Scholar 

  173. Thirthagiri, E., Robinson, C. M., Huntley, S., Davies, M., Yap, L. F., Prime, S. S., et al. (2007). Spindle assembly checkpoint and centrosome abnormalities in oral cancer. Cancer Letters, 258(2), 276–285. https://doi.org/10.1016/j.canlet.2007.09.008.

    Article  CAS  PubMed  Google Scholar 

  174. Lee, M. Y., Moreno, C. S., & Saavedra, H. I. (2014). E2F activators signal and maintain centrosome amplification in breast cancer cells. Molecular and Cellular Biology, 34(14), 2581–2599. https://doi.org/10.1128/MCB.01688-13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Guo, H. Q., Gao, M., Ma, J., Xiao, T., Zhao, L. L., Gao, Y., et al. (2007). Analysis of the cellular centrosome in fine-needle aspirations of the breast. Breast Cancer Research, 9(4), R48. https://doi.org/10.1186/bcr1752.

    Article  CAS  PubMed  Google Scholar 

  176. Caracciolo, V., D’Agostino, L., Draberova, E., Sladkova, V., Crozier-Fitzgerald, C., Agamanolis, D. P., et al. (2010). Differential expression and cellular distribution of gamma-tubulin and betaIII-tubulin in medulloblastomas and human medulloblastoma cell lines. Journal of Cellular Physiology, 223(2), 519–529. https://doi.org/10.1002/jcp.22077.

    Article  CAS  PubMed  Google Scholar 

  177. Sato, N., Mizumoto, K., Nakamura, M., Nakamura, K., Kusumoto, M., Niiyama, H., et al. (1999). Centrosome abnormalities in pancreatic ductal carcinoma. Clinical Cancer Research, 5(5), 963–970.

    CAS  PubMed  Google Scholar 

  178. Bayani, J., Paderova, J., Murphy, J., Rosen, B., Zielenska, M., & Squire, J. A. (2008). Distinct patterns of structural and numerical chromosomal instability characterize sporadic ovarian cancer. Neoplasia, 10(10), 1057–1065. https://doi.org/10.1593/neo.08584.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Shinmura, K., Tao, H., Nagura, K., Goto, M., Matsuura, S., Mochizuki, T., et al. (2011). Suppression of hydroxyurea-induced centrosome amplification by NORE1A and down-regulation of NORE1A mRNA expression in non-small cell lung carcinoma. Lung Cancer, 71(1), 19–27. https://doi.org/10.1016/j.lungcan.2010.04.006.

    Article  PubMed  Google Scholar 

  180. Perucca-Lostanlen, D., Rostagno, P., Grosgeorge, J., Marcie, S., Gaudray, P., & Turc-Carel, C. (2004). Distinct MDM2 and P14ARF expression and centrosome amplification in well-differentiated liposarcomas. Genes, Chromosomes & Cancer, 39(2), 99–109. https://doi.org/10.1002/gcc.10303.

    Article  CAS  Google Scholar 

  181. Rhys, A. D., Monteiro, P., Smith, C., Vaghela, M., Arnandis, T., Kato, T., et al. (2018). Loss of E-cadherin provides tolerance to centrosome amplification in epithelial cancer cells. The Journal of Cell Biology, 217(1), 195–209. https://doi.org/10.1083/jcb.201704102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Hsu, L. C., Kapali, M., DeLoia, J. A., & Gallion, H. H. (2005). Centrosome abnormalities in ovarian cancer. International Journal of Cancer, 113(5), 746–751. https://doi.org/10.1002/ijc.20633.

    Article  CAS  PubMed  Google Scholar 

  183. Singh, A., Denu, R. A., Wolfe, S. K., Sperger, J. M., Schehr, J., Witkowsky, T., et al. (2020). Centrosome amplification is a frequent event in circulating tumor cells from subjects with metastatic breast cancer. Molecular Oncology. https://doi.org/10.1002/1878-0261.12687.

  184. Hoque, A., Carter, J., Xia, W., Hung, M. C., Sahin, A. A., Sen, S., et al. (2003). Loss of aurora A/STK15/BTAK overexpression correlates with transition of in situ to invasive ductal carcinoma of the breast. Cancer Epidemiology, Biomarkers & Prevention, 12(12), 1518–1522.

    CAS  Google Scholar 

  185. Mayer, F., Stoop, H., Sen, S., Bokemeyer, C., Oosterhuis, J. W., & Looijenga, L. H. (2003). Aneuploidy of human testicular germ cell tumors is associated with amplification of centrosomes. Oncogene, 22(25), 3859–3866. https://doi.org/10.1038/sj.onc.1206469.

    Article  CAS  PubMed  Google Scholar 

  186. Del Rey, J., Prat, E., Ponsa, I., Lloreta, J., Gelabert, A., Algaba, F., et al. (2010). Centrosome clustering and cyclin D1 gene amplification in double minutes are common events in chromosomal unstable bladder tumors. BMC Cancer, 10, 280. https://doi.org/10.1186/1471-2407-10-280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Duensing, A., Chin, A., Wang, L., Kuan, S. F., & Duensing, S. (2008). Analysis of centrosome overduplication in correlation to cell division errors in high-risk human papillomavirus (HPV)-associated anal neoplasms. Virology, 372(1), 157–164. https://doi.org/10.1016/j.virol.2007.10.030.

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by a grant from the National Cancer Institute (U01 CA179671) to RA.

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Authors and Affiliations

  1. Department of Biology, Georgia State University, 100 Piedmont Ave, Atlanta, GA, 30303, USA

    Karuna Mittal, Jaspreet Kaur, Meghan Jaczko, Guanhao Wei & Ritu Aneja

  2. Department of Pathology, University of Nottingham and Nottingham University Hospitals, Nottingham, UK

    Michael S. Toss & Emad A. Rakha

  3. Department of Pathology, Stavanger University Hospital, Stavanger, Norway

    Emiel Adrianus Maria Janssen

  4. Department of Breast and Endocrine Surgery, Stavanger University Hospital, Stavanger, Norway

    Håvard Søiland

  5. Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University Hospital, Atlanta, GA, USA

    Omer Kucuk

  6. Department of Pathology, Emory University Hospital, Atlanta, GA, USA

    Michelle Dian Reid

  7. Chestatee Pathology, Atlanta, GA, USA

    Meenakshi V. Gupta

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Mittal, K., Kaur, J., Jaczko, M. et al. Centrosome amplification: a quantifiable cancer cell trait with prognostic value in solid malignancies. Cancer Metastasis Rev 40, 319–339 (2021). https://doi.org/10.1007/s10555-020-09937-z

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