Trends in Cell Biology
OpinionManaging the centrosome numbers game: from chaos to stability in cancer cell division
Section snippets
Centrosomes are microtubule-organizing centers
The dual and opposing nature of centrosomes in normal mitotic cells facilitates the assembly of a bipolar spindle and assures equal distribution of the replicated genome to each daughter cell. Moreover, this process provides each daughter with a single centrosome or microtubule-organizing center (MTOC) on which to rebuild a significant component of the cytoskeleton and reinitiate the next centrosome replication cycle. The regulatory mechanism (checkpoint) that assures that centrosomes divide
Molecular scenarios for the origin of supernumerary centrosomes
The centrosome cycle is initiated at the beginning of the G1 phase of the cell cycle, when each new daughter cell receives a single centrosome. Subsequently, when cells progress through S phase, the centrosome is duplicated such that two equal but opposing centrosomes can split apart and, at the end of G2, form opposite poles of the spindle. Closer examination by electron microscopy (EM) reveals that each centrosome contains a pair of centrioles surrounded by an electron-dense pericentriolar
Supernumerary centrosomes in established cell lines and human tumor cells
The earliest observation on centrosome abnormalities in tumor cell cultures came from EM and early immunofluorescence studies of neuroblastoma cells in vitro 18., 19., 20.. Using a newly discovered human autoimmune serum that specifically recognizes centrosomes, it was noted that N115 mouse neuroblastoma cells contained unusually large centrosomes containing as many as ten or more centrioles per centrosome (Fig. 1a–c). Yet during mitosis, the centrosomes were arranged into two large spindle
Corralling maverick centrosomes
How do cells control extra centrosomes and maintain numerical order of MTOCs during interphase and mitosis? It is known that some normal diploid cells have the capacity to dispense with the centrioles and centrosomes or initiate centrosome assembly de novo, at various stages of their life cycles 21., 22., 23.. The embryos of the surf clam, Spisula, can selectively turn off the paternally derived centrosome and diminish its ability to nucleate microtubules 23. Higher plant cells lack centrioles
Concluding remarks
Aneuploidy is a common feature of most human cancers and probably represents an early and significant event in tumorigenesis. The discovery of centrosome amplification in most human cancer cells and its one-to-one correlation with aneuploidy in colorectal tumors 9 suggest the following scenario for the initiation of a transformed cell focus within tissue.
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Extra centrosomes appear either through a mutation involving a component of the cell cycle checkpoint controlling centrosome duplication or
Acknowledgements
Thanks are extended to Ilia Ouspenski and Thea Goepfert for helpful discussions and critical reading of the manuscript, Frank Herbert for help with the illustrations, and Betty Ledlie and Michael Wise for editorial assistance. Supported by RO1 grant CA-41424 to B.R.B. and PO1 grant CA-64255 to Daniel Medina and by the National Cancer Institute, NIH.
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2021, Current Opinion in Structural BiologyCitation Excerpt :A direct and obvious consequence of having more than two centrosomes in a mitotic cell is the possibility to assemble a multipolar spindle that generates daughter cells with dramatic changes in chromosome numbers and therefore decreased viability [17,18]. To avoid cell death, cancer cells with extra centrosomes actively cluster them into two functional spindle poles promoting bipolar or pseudo-bipolar anaphases, which generate only moderate chromosome segregation errors and more importantly remain viable [17–22]. Molecular players identified in different screens [18,23] such as KIFC1/HSET, a minus-end directed kinesin, became attractive candidates for therapeutic approaches.
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