Cells with multiple centrosomes rarely undergo multipolar cell divisions, and when they do occur, the progeny of these divisions are typically inviable. This low frequency of viable multipolar divisions means multipolar divisions cannot account for the observed rates of chromosomal instability in CIN cells. [@ganem_mechanism_2009]
Definitions
Synthesis
While multipolar cell division can theoretically result from the presence of extra centrosomes in cells, these divisions are uncommon because cells with supernumerary centrosomes typically cluster their centrosomes to undergo bipolar rather than multipolar divisions. The rarity of multipolar divisions appears to be driven by selection against the aneuploid progeny they generate, as chromosome missegregation alone is insufficient for aneuploid cell propagation and compromises the proliferation capacity of diploid cells. Instead, extra centrosomes promote chromosome missegregation primarily during bipolar division through mechanisms such as transient multipolar spindle intermediates that allow merotelic attachments to accumulate, thereby generating chromosomal instability without the need for completing multipolar division. What remains less clear is whether the inviability of multipolar division progeny reflects an absolute inability to tolerate the extreme aneuploidy resulting from tripartite or higher-order chromosome segregation, or whether rare progeny could survive with additional phenotypic changes that permit propagation of highly aneuploid karyotypes.
Related
- Stat1 inactivation mechanism is conserved between mouse and human aneuploid cancers
- Mps1 truncation-induced CIN generates convergent recurrent chromosome gains
- Aneuploidy increases spontaneous tumor formation in aged animals
- Increased aneuploidy inhibits chemically and genetically induced tumorigenesis
- Aneuploid tumors inactivate Stat1 signaling with increased Myc activity
- Extra centrosomes correlate with chromosomal instability in tumors
- Stat1 loss combined with Myc activation alleviates CIN-induced immune infiltration
- Extra centrosomes promote chromosome missegregation during bipolar division
- CIN exists independently of classic mitotic defects in most cells
- Single-cell sequencing reveals karyotype heterogeneity in lymphomas
- Aneuploidy exhibits dual roles as oncogenic and tumor-suppressive
- CIN causality toward aneuploidy was previously unanswered
- CENP-E reduction generates aneuploidy and chromosomal instability
- Missegregation alone insufficient for aneuploid cell propagation