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Mitotic spindle multipolarity without centrosome amplification

Abstract

Mitotic spindle bipolarity is essential for faithful segregation of chromosomes during cell division. Multipolar spindles are often seen in human cancers and are usually associated with supernumerary centrosomes that result from centrosome overduplication or cytokinesis failure. A less-understood path to multipolar spindle formation may arise due to loss of spindle pole integrity in response to spindle and/or chromosomal forces. Here we discuss the different routes leading to multipolar spindle formation, focusing on spindle multipolarity without centrosome amplification. We also present the distinct and common features between these pathways and discuss their therapeutic implications.

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Figure 1: A schematic summary of the main causes of mitotic spindle multipolarity with and without centrosome amplification.
Figure 2: Images illustrating mitotic spindle multipolarity with and without centrosome amplification.
Figure 3: The role of misaligned chromosomes and chromatids in multipolar spindle formation due to loss of spindle pole integrity.

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Acknowledgements

We thank Beth Weaver and Francesca Degrassi for communicating results before publication. We apologise to all colleagues whose primary work could not be cited due to length restrictions. E.L. is supported by Programa Operacional Regional do Norte (ON.2) and grants NORTE-07-0124-FEDER-000003 and PTDC/SAU-OBD/100261/2008 from Fundação para a Ciência e a Tecnologia (FCT) of Portugal (COMPETE-FEDER). Work in the laboratory of H.M is funded by FEDER through the Operational Competitiveness Programme – COMPETE and by National Funds through FCT – Fundação para a Ciência e a Tecnologia under the project FCOMP-01-0124-FEDER-015941 (PTDC/SAU-ONC/112917/2009), the Human Frontier Science Program and the 7th framework program grant PRECISE from the European Research Council.

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Correspondence to Helder Maiato or Elsa Logarinho.

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Summary of conditions, including loss of protein function and drug treatment, that are described to lead to loss of spindle pole integrity (PDF 166 kb)

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Maiato, H., Logarinho, E. Mitotic spindle multipolarity without centrosome amplification. Nat Cell Biol 16, 386–394 (2014). https://doi.org/10.1038/ncb2958

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