The spindle assembly checkpoint: perspectives in tumorigenesis and cancer therapy

Abstract

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.

Keywords

spindle assembly checkpoint / mitosis / chromosome instability / tumor / cancer therapy

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