Spindle Multipolarity Is Prevented by Centrosomal Clustering

• Published in: Science (American Association for the Advancement of Science) Vol. 307; no. 5706; pp. 127 - 129
• Main Authors: Quintyne, Nicholas J, Reing, Janet E, Hoffelder, Diane R, Gollin, Susanne M, Saunders, William S
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 07.01.2005; The American Association for the Advancement of Science
• 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; Enzyme; Genomics; Hydrolases; Chromosome; Instability; Dynein ATPase; Microtubule; Molecular motor; Centrosome
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1104905

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.