纺锤体检查点生物学特性与肿瘤

摘要

纺锤体检查点是在细胞有丝分裂期保证染色体正确分离的重要监控机制,维持着基因组稳定性.纺锤体检查点的分子调控机制已逐步明确,许多肿瘤细胞存在纺锤体检查点功能缺陷,纺锤体检查点表达量的失调、基因单核苷酸多态性及启动子甲基化等可能与其功能异常有关.抗肿瘤药物通过影响纺锤体检查点的表达而启动杀伤肿瘤效应.深入了解肿瘤纺锤体检查点调控机制,有助于发现新的杀灭肿瘤细胞的靶向化疗药物.%The spindle checkpoint is an important cell-cycle surveillance mechanism that ensures the fidelity of chromosome segregation during mitosis and is required for genetic stability. It has become increasingly clear that malfunction of the cell-cycle surveillance mechanism involving the spindle checkpoint contributes to cancer formation.Accumulated evidence shows that deregulated expression, genotypic polymorphism or promoter methylation of the mitotic checkpoint components are associated with tumourigenesis. Anti-cancer drugs disrupt the normal function of the mitotic spindle and cause spindle checkpoint-mediated mitotic arrest and/or apoptosis. Delineating the precise regulatory mechanisms of the spindle checkpoint will provide novel effective strategies in anticancer treatment.