The spindle assembly checkpoint: perspectives in tumorigenesis and cancer therapy
Received date: 30 Nov 2010
Accepted date: 24 Dec 2010
Published date: 01 Apr 2011
Copyright
Loss or gain of chromosomes, a condition known as aneuploidy, is a common feature of tumor cells and has therefore been proposed as the driving force for tumorigenesis. Such chromosomal instability can arise during mitosis as a result of mis-segregation of the duplicated sister chromatids to the two daughter cells. In normal cells, mis-segregation is usually prevented by the spindle assembly checkpoint (SAC), a sophisticated surveillance mechanism that inhibits mitotic exit until all chromosomes have successfully achieved bipolar attachment to spindle microtubules. Complete abrogation of SAC activity is lethal to normal as well as to tumor cells, as a consequence of massive chromosome mis-segregation. Importantly, many human aneuploid tumor cells exhibit a weakened SAC activity that allows them to tolerate gains or losses of a small number of chromosomes; and interfering with this SAC residual activity may constitute a suitable strategy to kill cancer cells. This review focuses on the potential link between SAC and tumorigenesis, and the therapeutic strategy to target the SAC for cancer treatment.
Key words： spindle assembly checkpoint; mitosis; chromosome instability; tumor; cancer therapy
Joana BARBOSA , Ana Vanessa NASCIMENTO , Juliana FARIA , Patrícia SILVA , Hassan BOUSBAA . The spindle assembly checkpoint: perspectives in tumorigenesis and cancer therapy[J]. Frontiers in Biology, 2011 , 6(2) : 147 -155 . DOI: 10.1007/s11515-011-1122-x
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