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http://dx.doi.org/10.14348/molcells.2021.0220

Generation and Fates of Supernumerary Centrioles in Dividing Cells  

Shin, Byungho (Department of Biological Sciences, Seoul National University)
Kim, Myung Se (Department of Biological Sciences, Seoul National University)
Lee, Yejoo (Department of Biological Sciences, Seoul National University)
Jung, Gee In (Department of Biological Sciences, Seoul National University)
Rhee, Kunsoo (Department of Biological Sciences, Seoul National University)
Publication Information
Molecules and Cells / v.44, no.10, 2021 , pp. 699-705 More about this Journal
Abstract
The centrosome is a subcellular organelle from which a cilium assembles. Since centrosomes function as spindle poles during mitosis, they have to be present as a pair in a cell. How the correct number of centrosomes is maintained in a cell has been a major issue in the fields of cell cycle and cancer biology. Centrioles, the core of centrosomes, assemble and segregate in close connection to the cell cycle. Abnormalities in centriole numbers are attributed to decoupling from cell cycle regulation. Interestingly, supernumerary centrioles are commonly observed in cancer cells. In this review, we discuss how supernumerary centrioles are generated in diverse cellular conditions. We also discuss how the cells cope with supernumerary centrioles during the cell cycle.
Keywords
cancer cells; cell cycle; centrosome; mitosis; supernumerary centrioles;
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1 Vitre, B., Holland, A.J., Kulukian, A., Shoshani, O., Hirai, M., Wang, Y., Maldonado, M., Cho, T., Boubaker, J., Swing, D.A., et al. (2015). Chronic centrosome amplification without tumorigenesis. Proc. Natl. Acad. Sci. U. S. A. 112, E6321-E6330.
2 Raff, J.W. and Basto, R. (2017). Centrosome amplification and cancer: a question of sufficiency. Dev. Cell 40, 217-218.   DOI
3 Sala, R., Farrell, K.C., and Stearns, T. (2020). Growth disadvantage associated with centrosome amplification drives population-level centriole number homeostasis. Mol. Biol. Cell 31, 2646-2656.   DOI
4 Seo, M.Y., Jang, W., and Rhee, K. (2015). Integrity of the pericentriolar material is essential for maintaining centriole association during M phase. PLoS One 10, e0138905.   DOI
5 Potapova, T.A., Seidel, C.W., Box, A.C., Rancati, G., and Li, R. (2016). Transcriptome analysis of tetraploid cells identifies cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53. Mol. Biol. Cell 27, 3065-3084.   DOI
6 Antao, N.V., Marcet-Ortega, M., Cifani, P., Kentsis, A., and Foley, E.A. (2019). A cancer-associated missense mutation in PP2A-Aα increases centrosome clustering during mitosis. iScience 19, 74-82.   DOI
7 Balczon, R., Bao, L., Zimmer, W.E., Brown, K., Zinkowski, R.P., and Brinkley, B.R. (1995). Dissociation of centrosome replication events from cycles of DNA synthesis and mitotic division in hydroxyurea-arrested Chinese hamster ovary cells. J. Cell Biol. 130, 105-115.   DOI
8 Basto, R., Brunk, K., Vinadogrova, T., Peel, N., Franz, A., Khodjakov, A., and Raff, J.W. (2008). Centrosome amplification can initiate tumorigenesis in flies. Cell 133, 1032-1042.   DOI
9 Chan, J.Y. (2011). A clinical overview of centrosome amplification in human cancers. Int. J. Biol. Sci. 7, 1122-1144.   DOI
10 Coelho, P.A., Bury, L., Shahbazi, M.N., Liakath-Ali, K., Tate, P.H., Wormald, S., Hindley, C.J., Huch, M., Archer, J., Skarnes, W.C., et al. (2015). Overexpression of Plk4 induces centrosome amplification, loss of primary cilia and associated tissue hyperplasia in the mouse. Open Biol. 5, 150209.   DOI
11 Drosopoulos, K., Tang, C., Chao, W.C.H., and Linardopoulos, S. (2014). APC/C is an essential regulator of centrosome clustering. Nat. Commun. 5, 3686.   DOI
12 Fan, G., Sun, L., Shan, P., Zhang, X., Huan, J., Zhang, X., Li, D., Wang, T., Wei, T., Zhang, X., et al. (2015). Loss of KLF14 triggers centrosome amplification and tumorigenesis. Nat. Commun. 6, 8450.   DOI
13 Inanc, B., Dodson, H., and Morrison, C.G. (2010). A centrosome-autonomous signal that involves centriole disengagement permits centrosome duplication in G2 phase after DNA damage. Mol. Biol. Cell 21, 3866-3877.   DOI
14 Ganem, N.J., Godinho, S.A., and Pellman, D. (2009). A mechanism linking extra centrosomes to chromosomal instability. Nature 460, 278-282.   DOI
15 Levine, M.S., Bakker, B., Boeckx, B., Moyett, J., Lu, J., Vitre, B., Spierings, D.C., Lansdorp, P.M., Cleveland, D.W., Lambrechts, D., et al. (2017). Centrosome amplification is sufficient to promote spontaneous tumorigenesis in mammals. Dev. Cell 40, 313-322.e5.   DOI
16 Liao, Z., Zhang, H., Fan, P., Huang, Q., Dong, K., Qi, Y., Song, J., Chen, L., Liang, H., Chen, X., et al. (2019). High PLK4 expression promotes tumor progression and induces epithelial-mesenchymal transition by regulating the Wnt/β-catenin signaling pathway in colorectal cancer. Int. J. Oncol. 54, 479-490.
17 Krzywicka-Racka, A. and Sluder, G. (2011). Repeated cleavage failure does not establish centrosome amplification in untransformed human cells. J. Cell Biol. 194, 199-207.   DOI
18 Kwon, M., Bagonis, M., Danuser, G., and Pellman, D. (2015). Direct microtubule-binding by Myosin-10 orients centrosomes toward retraction fibers and subcortical actin clouds. Dev. Cell 34, 323-337.   DOI
19 Fukasawa, K., Choi, T., Kuriyama, R., Rulong, S., and Vande Woude, G.F. (1996). Abnormal centrosome amplification in the absence of p53. Science 271, 1744-1747.   DOI
20 Davoli, T. and de Lange, T. (2011). The causes and consequences of polyploidy in normal development and cancer. Annu. Rev. Cell Dev. Biol. 27, 585-610.   DOI
21 Larsson, L.I., Bjerregaard, B., and Talts, J.F. (2008). Cell fusions in mammals. Histochem. Cell Biol. 129, 551-561.   DOI
22 Fu, J., Lipinszki, Z., Rangone, H., Min, M., Mykura, C., Chao-Chu, J., Schneider, S., Dzhindzhev, N.S., Gottardo, M., Riparbelli, M.G., et al. (2016). Conserved molecular interactions in centriole-to-centrosome conversion. Nat. Cell Biol. 18, 87-99.   DOI
23 Lambrus, B.G. and Holland, A.J. (2017). A new mode of mitotic surveillance. Trends Cell Biol. 27, 314-321.   DOI
24 Lee, K. and Rhee, K. (2012). Separase-dependent cleavage of pericentrin B is necessary and sufficient for centriole disengagement during mitosis. Cell Cycle 11, 2476-2485.   DOI
25 Loncarek, J., Hergert, P., and Khodjakov, A. (2010). Centriole reduplication during prolonged interphase requires procentriole maturation governed by Plk1. Curr. Biol. 20, 1277-1282.   DOI
26 Burigotto, M., Mattivi, A., Migliorati, D., Magnani, G., Valentini, C., Roccuzzo, M., Offterdinger, M., Pizzato, M., Schmidt, A., Villunger, A., et al. (2021). Centriolar distal appendages activate the centrosomePIDDosome-p53 signalling axis via ANKRD26. EMBO J. 40, e104844.
27 Kwon, M., Godinho, S.A., Chandhok, N.S., Ganem, N.J., Azioune, A., Thery, M., and Pellman, D. (2008). Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes. Genes Dev. 22, 2189-2203.   DOI
28 Quintyne, N.J., Reing, J.E., Hoffelder, D.R., Gollin, S.M., and Saunders, W.S. (2005). Spindle multipolarity is prevented by centrosomal clustering. Science 307, 127-129.   DOI
29 Reider, C.L. (2011). Mitosis in vertebrates: the G2/M and M/A transitions and their associated checkpoints. Chromosome Res. 19, 291-306.   DOI
30 Leber, B., Maier, B., Fuchs, F., Chi, J., Riffel, P., Anderhub, S., Wagner, L., Ho, A.D., Salisbury, J.L., Boutros, M., et al. (2010). Proteins required for centrosome clustering in cancer cells. Sci. Transl. Med. 2, 33ra38.   DOI
31 Dikovskaya, D., Schiffmann, D., Newton, I.P., Oakley, A., Kroboth, K., Sansom, O., Jamieson, T.J., Meniel, V., Clarke, A., and Nathke, I.S. (2007). Loss of APC induces polyploidy as a result of a combination of defects in mitosis and apoptosis. J. Cell Biol. 176, 183-195.   DOI
32 Dzhindzhev, N.S., Tzolovsky, G., Lipinszki, Z., Schneider, S., Lattao, R., Fu, J., Debski, J., Dadlez, M., and Glover, D.M. (2014). Plk4 phosphorylates Ana2 to trigger Sas6 recruitment and procentriole formation. Curr. Biol. 24, 2526-2532.   DOI
33 Marthiens, V., Rujano, M.A., Pennetier, C., Tessier, S., Paul-Gilloteaux, P., and Basto, R. (2013). Centrosome amplification causes microcephaly. Nat. Cell Biol. 15, 731-740.   DOI
34 McCoy, R.C., Demko, Z., Ryan, A., Banjevic, M., Hill, M., Sigurjonssen, S., Robinowitz, M., Fraser, H., and Petrov, D.A. (2015). Common variants spanning PLK4 are associated with mitotic-origin aneuploidy in human embryos. Science 348, 235-238.   DOI
35 Nigg, E.A. and Holland, A.J. (2018). Once and only once: mechanisms of centriole duplication and their deregulation in disease. Nat. Rev. Mol. Cell Biol. 19, 297-312.   DOI
36 Nigg, E.A. and Raff, J.W. (2009). Centrioles, centrosomes, and cilia in health and disease. Cell 139, 663-678.   DOI
37 Kong, D., Sahabandu, N., Sullenberger, C., Vasquez-Limeta, A., Luvsanjav, D., Lukasik, K., and Loncarek, J. (2020). Prolonged mitosis results in structurally aberrant and over-elongated centrioles. J. Cell Biol. 219, e201910019.   DOI
38 Kim, J., Kim, J., and Rhee, K. (2019). PCNT is critical for the association and conversion of centrioles to centrosomes during mitosis. J. Cell Sci. 132, jcs225789.   DOI
39 Kim, J., Lee, K., and Rhee, K. (2015). PLK1 regulation of PCNT cleavage ensures fidelity of centriole separation during mitotic exit. Nat. Commun. 6, 10076.   DOI
40 Kohlmaier, G., Loncarek, J., Meng, X., McEwen, B.F., Mogensen, M.M., Spektor, A., Dynlacht, B.D., Khodjakov, A., and Gonczy, P. (2009). Overly long centrioles and defective cell division upon excess of the SAS-4-related protein CPAP. Curr. Biol. 19, 1012-1018.   DOI
41 Kulukian, A., Holland, A.J., Vitre, B., Naik, S., Cleveland, D.W., and Fuchs, E. (2015). Epidermal development, growth control, and homeostasis in the face of centrosome amplification. Proc. Natl. Acad. Sci. U. S. A. 112, E6311-E6320.
42 Ganier, O., Schnerch, D., Oertle, P., Lim, R.Y., Plodinec, M., and Nigg, E.A. (2018). Structural centrosome aberrations promote non-cell-autonomous invasiveness. EMBO J. 37, e98576.   DOI
43 Sabino, D., Gogendeau, D., Gambarotto, D., Nano, M., Pennetier, C., Dingli, F., Arras, G., Loew, D., and Basto, R. (2015). Moesin is a major regulator of centrosome behavior in epithelial cells with extra centrosomes. Curr. Biol. 25, 879-889.   DOI
44 Castellanos, E., Dominguez, P., and Gonzalez, C. (2008). Centrosome dysfunction in Drosophila neural stem cells causes tumors that are not due to genome instability. Curr. Biol. 18, 1209-1214.   DOI
45 O'Connell, K.F., Caron, C., Kopish, K.R., Hurd, D.D., Kemphues, K.J., Li, Y., and White, J.G. (2001). The C. elegans zyg-1 gene encodes a regulator of centrosome duplication with distinct maternal and paternal roles in the embryo. Cell 105, 547-558.   DOI
46 Ohta, M., Ashikawa, T., Nozaki, Y., Kozuka-Hata, H., Goto, H., Inagaki, M., Oyama, M., and Kitagawa, D. (2014). Direct interaction of Plk4 with STIL ensures formation of a single procentriole per parental centriole. Nat. Commun. 5, 5267.   DOI
47 Marteil, G., Guerrero, A., Vieira, A.F., de Almeida, B.P., Machado, P., Mendonca, S., Mesquita, M., Villarreal, B., Fonseca, I., Francia, M.E., et al. (2018). Over-elongation of centrioles in cancer promotes centriole amplification and chromosome missegregation. Nat. Commun. 9, 1258.   DOI
48 Edgar, B.A. and Orr-Weaver, T.L. (2001). Endoreplication cell cycles: more for less. Cell 105, 297-306.   DOI
49 Ganem, N.J., Cornils, H., Chiu, S.Y., O'Rourke, K.P., Arnaud, J., Yimlamai, D., Thery, M., Camargo, F.D., and Pellman, D. (2014). Cytokinesis failure triggers hippo tumor suppressor pathway activation. Cell 158, 833-848.   DOI
50 Godinho, S.A. and Pellman, D. (2014). Causes and consequences of centrosome abnormalities in cancer. Philos. Trans. R. Soc. Lond. B Biol. Sci. 369, 20130467.   DOI
51 Fava, L.L., Schuler, F., Sladky, V., Haschka, M.D., Soratroi, C., Eiterer, L., Demetz, E., Weiss, G., Geley, S., Nigg, E.A., et al. (2017). The PIDDosome activates p53 in response to supernumerary centrosomes. Genes Dev. 31, 34-45.   DOI
52 Sullenberger, C., Vasquez-Limeta, A., Kong, D., and Loncarek, J. (2020). With age comes maturity: biochemical and structural transformation of a human centriole in the making. Cells 9, 1429.   DOI
53 Kuznetsova, A.Y., Seget, K., Moeller, G.K., de Pagter, M.S., de Roos, J.A., Durrbaum, M., Kuffer, C., Muller, S., Zaman, G.J., Kloosterman, W.P., et al. (2015). Chromosomal instability, tolerance of mitotic errors and multidrug resistance are promoted by tetraploidization in human cells. Cell Cycle 14, 2810-2820.   DOI
54 Lambrus, B.G., Daggubati, V., Uetake, Y., Scott, P.M., Clutario, K.M., Sluder, G., and Holland, A.J. (2016). A USP28-53BP1-p53-p21 signaling axis arrests growth after centrosome loss or prolonged mitosis. J. Cell Biol. 214, 143-153.   DOI
55 Schmidt, T.I., Kleylein-Sohn, J., Westendorf, J., Le Clech, M., Lavoie, S.B., Stierhof, Y.D., and Nigg, E.A. (2009). Control of centriole length by CPAP and CP110. Curr. Biol. 19, 1005-1011.   DOI
56 Schnerch, D. and Nigg, E.A. (2016). Structural centrosome aberrations favor proliferation by abrogating microtubule-dependent tissue integrity of breast epithelial mammospheres. Oncogene 35, 2711-2722.   DOI
57 Sercin, O., Larsimont, J.C., Karambelas, A.E., Marthiens, V., Moers, V., Boeckx, B., Le Mercier, M., Lambrechts, D., Basto, R., and Blanpain, C. (2016). Transient PLK4 overexpression accelerates tumorigenesis in p53-deficient epidermis. Nat. Cell Biol. 18, 100-110.   DOI
58 Tsou, M.F. and Stearns, T. (2006). Mechanism limiting centrosome duplication to once per cell cycle. Nature 442, 947-951.   DOI
59 Tsuchiya, Y., Yoshiba, S., Gupta, A., Watanabe, K., and Kitagawa, D. (2016). Cep295 is a conserved scaffold protein required for generation of a bona fide mother centriole. Nat. Commun. 7, 12567.   DOI
60 Galipeau, P.C., Cowan, D.S., Sanchez, C.A., Barrett, M.T., Emond, M.J., Levine, D.S., Rabinovitch, P.S., and Reid, B.J. (1996). 17p (p53) allelic losses, 4N (G2/tetraploid) populations, and progression to aneuploidy in Barrett's esophagus. Proc. Natl. Acad. Sci. U. S. A. 93, 7081-7084.   DOI
61 Galofre, C., Asensio, E., Ubach, M., Torres, I.M., Quintanilla, I., Castells, A., and Camps, J. (2020). Centrosome reduction in newly-generated tetraploid cancer cells obtained by separase depletion. Sci. Rep. 10, 9152.   DOI
62 Wu, Q., Yu, X., Liu, L., Sun, S., and Sun, S. (2021). Centrosome-phagy: implications for human diseases. Cell Biosci. 11, 49.   DOI
63 Wang, W.J., Soni, R.K., Uryu, K., and Tsou, M.F. (2011). The conversion of centrioles to centrosomes: essential coupling of duplication with segregation. J. Cell Biol. 193, 727-739.   DOI
64 Watanabe, Y., Honda, S., Konishi, A., Arakawa, S., Murohashi, M., Yamaguchi, H., Torii, S., Tanabe, M., Tanaka, S., Warabi, E., et al. (2016). Autophagy controls centrosome number by degrading Cep63. Nat. Commun. 7, 13508.   DOI
65 Wong, C. and Stearns, T. (2003). Centrosome number is controlled by a centrosome-intrinsic block to reduplication. Nat. Cell Biol. 5, 539-544.   DOI
66 Chiba, S., Okuda, M., Mussman, J.G., and Fukasawa, K. (2000). Genomic convergence and suppression of centrosome hyperamplification in primary p53-/- cells in prolonged culture. Exp. Cell Res. 258, 310-321.   DOI
67 Bettencourt-Dias, M., Rodrigues-Martins, A., Carpenter, L., Riparbelli, M., Lehmann, L., Gatt, M.K., Carmo, N., Balloux, F., Callaini, G., and Glover, D.M. (2005). SAK/PLK4 is required for centriole duplication and flagella development. Curr. Biol. 15, 2199-2207.   DOI
68 Cabral, G., Sans, S.S., Cowan, C.R., and Dammermann, A. (2013). Multiple mechanisms contribute to centriole separation in C. elegans. Curr. Biol. 23, 1380-1387.   DOI
69 Chang, J., Cizmecioglu, O., Hoffmann, I., and Rhee, K. (2010). PLK2 phosphorylation is critical for CPAP function in procentriole formation during the centrosome cycle. EMBO J. 29, 2395-2406.   DOI
70 Baudoin, N.C., Nicholson, J.M., Soto, K., Martin, O., Chen, J., and Cimini, D. (2020). Asymmetric clustering of centrosomes defines the early evolution of tetraploid cells. Elife 9, e54565.   DOI
71 Matsuo, K., Ohsumi, K., Iwabuchi, M., Kawamata, T., Ono, Y., and Takahashi, M. (2012). Kendrin is a novel substrate for separase involved in the licensing of centriole duplication. Curr. Biol. 22, 915-921.   DOI
72 Jung, G.I. and Rhee, K. (2021). Triple deletion of TP53, PCNT, and CEP215 promotes centriole amplification in the M phase. Cell Cycle 20, 1500-1517.   DOI
73 Zack, T.I., Schumacher, S.E., Carter, S.L., Cherniack, A.D., Saksena, G., Tabak, B., Lawrence, M.S., Zhsng, C.Z., Wala, J., Mermel, C.H., et al. (2013). Pan-cancer patterns of somatic copy number alteration. Nat. Genet. 45, 1134-1140.   DOI
74 Godinho, S.A., Picone, R., Burute, M., Dagher, R., Su, Y., Leung, C.T., Polyak, K., Brugge, J.S., Thery, M., and Pellman, D. (2014). Oncogene-like induction of cellular invasion from centrosome amplification. Nature 510, 167-171.   DOI
75 Habedanck, R., Stierhof, Y.D., Wilkinson, C.J., and Nigg, E.A. (2005). The Polo kinase Plk4 functions in centriole duplication. Nat. Cell Biol. 7, 1140-1146.   DOI
76 Hirono, M. (2014). Cartwheel assembly. Philos. Trans. R. Soc. Lond. B Biol. Sci. 369, 20130458.   DOI
77 Holland, A.J. and Cleveland, D.W. (2009). Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis. Nat. Rev. Mol. Cell Biol. 10, 478-487.   DOI
78 Olaharski, A.J., Sotelo, R., Solorza-Luna, G., Gonsebatt, M.E., Guzman, P., Mohar, A., and Eastmond, D.A. (2006). Tetraploidy and chromosomal instability are early events during cervical carcinogenesis. Carcinogenesis 27, 337-343.   DOI
79 Shukla, A., Kong, D., Sharma, M., Magidson, V., and Loncarek, J. (2015). Plk1 relieves centriole block to reduplication by promoting daughter centriole maturation. Nat. Commun. 6, 8077.   DOI
80 Kleylein-Sohn, J., Westendorf, J., Le Clech, M., Habedanck, R., Stierhof, Y.D., and Nigg, E.A. (2007). Plk4-induced centriole biogenesis in human cells. Dev. Cell 13, 190-202.   DOI
81 Nigg, E.A. (2006). Origins and consequences of centrosome abberations in human cancers. Int. J. Cancer 119, 2717-2723.   DOI
82 Pihan, G.A., Wallace, J., Zhou, Y., and Doxsey, S.J. (2003). Centrosome abnormalities and chromosome instability occur together in pre-invasive carcinomas. Cancer Res. 63, 1398-1404.
83 Mikeladze-Dvali, T., von Tobel, L., Strnad, P., Knott, G., Leonhardt, H., Schermelleh, L., and Gonczy, P. (2012). Analysis of centriole elimination during C. elegans oogenesis. Development 139, 1670-1679.   DOI