Spindle multipolarity is prevented by centrosomal clustering.
Most tumor cells are characterized by increased genomic instability and chromosome segregational defects, often associated with hyperamplification of the centrosome and the formation of multipolar spindles. However, extra centrosomes do not always lead to multipolarity. Here, we describe a process of centrosomal clustering that prevented the formation of multipolar spindles in noncancer cells. Noncancer cells needed to overcome this clustering mechanism to allow multipolar spindles to form at a high frequency. The microtubule motor cytoplasmic dynein was a critical part of this coalescing machinery, and in some tumor cells overexpression of the spindle protein NuMA interfered with dynein localization, promoting multipolarity.
Quintyne
Nicholas J
NJ
Department of Biological Sciences, University of Pittsburgh, 4249 Fifth Avenue, Pittsburgh, PA 15260, USA.
Reing
Janet E
JE
Hoffelder
Diane R
DR
Gollin
Susanne M
SM
Saunders
William S
WS
D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D002460:Cell Line; D045744:Cell Line, Tumor; D018385:Centrosome / Q000502:physiology*; D003703:Demecolcine / Q000494:pharmacology; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D008941:Spindle Apparatus / Q000502:physiology*; D014162:Transfection
D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D004398:Dyneins; D003703:Demecolcine