Asymmetric Centriole Numbers at Spindle Poles Cause Chromosome Missegregation in Cancer

Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): Marco R. Cosenza, Anna Cazzola, Annik Rossberg, Nicole L. Schieber, Gleb Konotop, Elena Bausch, Alla Slynko, Tim Holland-Letz, Marc S. Raab, Taronish Dubash, Hanno Glimm, Sven Poppelreuther, Christel Herold-Mende, Yannick Schwab, Alwin Krämer
Chromosomal instability is a hallmark of cancer and correlates with the presence of extra centrosomes, which originate from centriole overduplication. Overduplicated centrioles lead to the formation of centriole rosettes, which mature into supernumerary centrosomes in the subsequent cell cycle. While extra centrosomes promote chromosome missegregation by clustering into pseudo-bipolar spindles, the contribution of centriole rosettes to chromosome missegregation is unknown. We used multi-modal imaging of cells with conditional centriole overduplication to show that mitotic rosettes in bipolar spindles frequently harbor unequal centriole numbers, leading to biased chromosome capture that favors binding to the prominent pole. This results in chromosome missegregation and aneuploidy. Rosette mitoses lead to viable offspring and significantly contribute to progeny production. We further show that centrosome abnormalities in primary human malignancies frequently consist of centriole rosettes. As asymmetric centriole rosettes generate mitotic errors that can be propagated, rosette mitoses are sufficient to cause chromosome missegregation in cancer.

Graphical abstract

Teaser

Extra centrosomes are frequent in human cancers and cause chromosome missegregation via clustering into a pseudo-bipolar mitotic spindle array. Cosenza et al. now demonstrate that centriole rosettes, a transient stage of extra centrosome formation, drive chromosome missegregation in addition to centrosome clustering and are frequently found in primary tumors.


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