Centrosomes and cancer: how cancer cells divide with too many centrosomes.
Precise control of centrosome number is crucial for bipolar spindle assembly and accurate transmission of genetic material to daughter cells. Failure to properly control centrosome number results in supernumerary centrosomes, which are frequently found in cancer cells. This presents a paradox: during mitosis, cells with more than two centrosomes are prone to multipolar mitoses and cell death, however, cancer cells possessing extra centrosomes usually divide successfully. One mechanism frequently utilized by cancer cells to escape death caused by multipolar mitoses is the clustering of supernumerary centrosomes into bipolar arrays. An understanding of the molecular mechanisms by which cancer cells can suppress multipolar mitoses is beginning to emerge. Here, we review what's currently known about centrosome clustering mechanisms and discuss potential strategies to target these mechanisms for the selective killing of cancer cells.
Godinho
Susana A
SA
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Kwon
Mijung
M
Pellman
David
D
D000818:Animals; D002448:Cell Adhesion; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018385:Centrosome / Q000648:ultrastructure*; D016678:Genome; D006801:Humans; D008938:Mitosis; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology*; D011003:Ploidies; D015398:Signal Transduction; D008941:Spindle Apparatus