Mechanisms and Consequences of Centrosome Clustering in Cancer Cells - The Centrosome - page 277

Fig. 17.2 Mechanisms leading to supernumerary centrioles/centrosomes. Centriole overduplication,
and de novo formation results in cells with an undefined number of extra centrioles, whereas cell
fusion, mitotic skipping as well as cleavage failure not only lead to a doubled centrosome number but
also to a duplicated DNA content. In contrast to overduplication, de novo formation, mitotic skipping,
and cleavage failure, cell fusion is not restricted to a defined cell cycle phase. Both overduplication and
de novo centriole formation are assumed to take place during S-phase. Cleavage failure and mitotic
skipping occur in G 2 /M, whereas the first event follows anaphase, the latter is not limited to a specific
mitotic phase (Adopted from Anderhub et al. 2012 )
PLK4 and CPAP to centrioles and thus in the initiation of centriole duplication in
human cells (Cizmecioglu et al. 2010 ; Dzhindzhev et al. 2010 ; Hatch et al. 2010 )
Abnormalities of diverse tumor suppressors and oncogenes can cause centrosome
amplification (Fukasawa 2007 ), which occurs through centrosome over-duplication
during interphase, de novo synthesis of centrosomes or cytokinesis failure (Nigg 2002)
(Fig. 17.2 ). Centrosome amplification is frequent in cancer, and is linked to tumori-
genesis and aneuploidy (Nigg 2002 ;Lingleetal. 1998 ; Pihan et al. 1998 ; Neben et al.
2003 ;Krämeretal. 2003 ; Koutsami et al. 2006 ). The extent of centrosomal aberrations