Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes.
Multiple centrosomes in tumor cells create the potential for multipolar divisions that can lead to aneuploidy and cell death. Nevertheless, many cancer cells successfully divide because of mechanisms that suppress multipolar mitoses. A genome-wide RNAi screen in Drosophila S2 cells and a secondary analysis in cancer cells defined mechanisms that suppress multipolar mitoses. In addition to proteins that organize microtubules at the spindle poles, we identified novel roles for the spindle assembly checkpoint, cortical actin cytoskeleton, and cell adhesion. Using live cell imaging and fibronectin micropatterns, we found that interphase cell shape and adhesion pattern can determine the success of the subsequent mitosis in cells with extra centrosomes. These findings may identify cancer-selective therapeutic targets: HSET, a normally nonessential kinesin motor, was essential for the viability of certain extra centrosome-containing cancer cells. Thus, morphological features of cancer cells can be linked to unique genetic requirements for survival.
Kwon
Mijung
M
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Godinho
Susana A
SA
Chandhok
Namrata S
NS
Ganem
Neil J
NJ
Azioune
Ammar
A
Thery
Manuel
M
Pellman
David
D
D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division; D002460:Cell Line; D016764:Cell Polarity; D048430:Cell Shape; D018385:Centrosome / Q000378:metabolism*; D003599:Cytoskeleton / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics; D016678:Genome; D007399:Interphase / Q000502:physiology; D016547:Kinesins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D034741:RNA, Small Interfering / Q000494:pharmacology; D008941:Spindle Apparatus
D000199:Actins; D029721:Drosophila Proteins; D034741:RNA, Small Interfering; D016547:Kinesins