The spindle assembly checkpoint: perspectives in tumorigenesis and cancer therapy |
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Authors: | Joana Barbosa Ana Vanessa Nascimento Juliana Faria Patr��cia Silva Hassan Bousbaa |
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Institution: | Centro de Investigacao em Ciencias da Saúde(CICS), Institute Superior de Ciencias da Saúde- Norte, CESPU, Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Portugal |
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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, missegregation 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. |
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Keywords: | spindle assembly checkpoint mitosis chromosome instability tumor cancer therapy |
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