Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes.

By M. Kwon, S. Godinho, N. Chandhok, Neil J. Ganem, Ammar Azioune, Manuel Théry, D. Pellman. Genes & Development, 2008

684 citations recorded by the source corpus.

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.

Subfields: Cell Biology

View Paper: https://www.semanticscholar.org/paper/9a8690e70db0e8cf17df511e186b0a4f651203cd

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In Cell Biology

1. Guido Kroemer
2. L. Galluzzi
3. J. Raff
4. Erich A. Nigg
5. Manuel Théry
6. S. Lens
7. R. Medema
8. E. Voest

Citations in the corpus

• Mitotic catastrophe: a mechanism for avoiding genomic instability (2011, background): “These proteins include KIFC1 (a Kinesin-14A family member also known as HSET”
• Radiation-induced cell death mechanisms (2010, background): “Several inhibitors are currently investigated in pre-clinical and clinical studies including aurora kinases [137, 138], PLK1 [83, 136], survivin [139], and kinesin family members (KIF11, KIFC1) [ 140 , 141].”
• Shared and separate functions of polo-like kinases and aurora kinases in cancer (2010, background): “Cancer cells frequently have an aberrant number of centrosomes, making them prone to deleterious multipolar cell divisions when clustering of these supernumerary centrosomes is prevente”
• Micropatterning as a tool to decipher cell morphogenesis and functions (2010, background): “on Y-shaped micropatterns) and, thus, eventually dictates the proportion of multipolar and bipolar spindles in cancer cells (Kwon et al., 2008).”
• Centrioles, centrosomes, and cilia in health and disease. (2009, background): “so these cells are more dependent on a functional SAC than normal cells (Basto et al., 2008; Kwon et al., 2008; Yang et al., 2008).”