Mitotic checkpoint defects in human cancers and their implications to chemotherapy.
The mitotic checkpoint, also known as spindle assembly checkpoint, is to ensure accurate chromosome segregation by inducing mitotic arrest when errors occur in the spindle structure or in the alignment of the chromosomes on the spindle. Loss of mitotic checkpoint control is a common event in human cancer cells, which is thought to be responsible for chromosome instability frequently observed in cancer cells. Several reports have shown that cells with a defective mitotic checkpoint are more resistant to several types of anticancer drugs from microtubule disruptors to DNA damaging agents. In addition, inactivation of key mitotic checkpoint proteins such as BUB (budding uninhibited by benzimidazole) and MAD (mitotic arrest deficient ) is influential in drug resistance in mitotic checkpoint defective cancer cells. The mitotic checkpoint has also been linked to DNA damage response and a defective mitotic checkpoint confers cancer cells resistance to certain DNA damaging anticancer drugs. This review presents recent evidence on mitotic checkpoint defects in human cancers and their association with resistance to anticancer drugs. In addition, the clinical importance and potential therapeutic implications of targeting the mitotic checkpoint to reverse drug resistance in cancer cells are also discussed.
Wang
Xianghong
X
Department of Anatomy, Faculty of Medicine, The University of Hong Kong, Hong Kong. xhwang@hkucc.hku.hk
Cheung
Hiu Wing
HW
Chun
Abel C S
AC
Jin
Dong-Yan
DY
Wong
Yong-Chuan
YC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000737:chemistry; D020090:Chromosome Segregation; D004249:DNA Damage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008938:Mitosis; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction; D008941:Spindle Apparatus; D043823:Taxoids / Q000494:pharmacology
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D043823:Taxoids