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 o...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2005-01, Vol.307 (5706), p.127-129
Main Authors: Quintyne, Nicholas J, Reing, Janet E, Hoffelder, Diane R, Gollin, Susanne M, Saunders, William S
Format: Article
Language:English
Subjects:
Antibodies
Antigens, Nuclear
Biological and medical sciences
Cancer
Cell Line
Cell Line, Tumor
Cell lines
Cells
Centrosome
Centrosome - physiology
Centrosomes
Chromosomes
Demecolcine - pharmacology
Dynactin Complex
Dyneins - metabolism
Fundamental and applied biological sciences. Psychology
Genomics
HEK293 cells
Humans
Medical research
Metaphase
Microtubule-Associated Proteins - metabolism
Mitosis
Mitotic spindle apparatus
Molecular and cellular biology
Mouth neoplasms
Nuclear Matrix-Associated Proteins
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Plasmids
Proteins
RNA, Small Interfering - metabolism
Small interfering RNA
Spindle Apparatus - physiology
Transfection
Tumor cell line
Tumors
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1104905