Spanish National Cancer Research Centre, Madrid, Spain.
Cancer Cell. 2010 Dec 14;18(6):641-54. doi: 10.1016/j.ccr.2010.10.028.
Targeting mitotic exit has been recently proposed as a relevant therapeutic approach against cancer. By using genetically engineered mice, we show that the APC/C cofactor Cdc20 is essential for anaphase onset in vivo in embryonic or adult cells, including progenitor/stem cells. Ablation of Cdc20 results in efficient regression of aggressive tumors, whereas current mitotic drugs display limited effects. Yet, Cdc20 null cells can exit from mitosis upon inactivation of Cdk1 and the kinase Mastl (Greatwall). This mitotic exit depends on the activity of PP2A phosphatase complexes containing B55α or B55δ regulatory subunits. These data illustrate the relevance of critical players of mitotic exit in mammals and their implications in the balance between cell death and mitotic exit in tumor cells.
靶向有丝分裂后期已被最近提出作为一种相关的治疗方法对抗癌症。通过使用基因工程小鼠，我们表明 APC/C 辅助因子 Cdc20 在体内的胚胎或成年细胞，包括祖细胞/干细胞，有丝分裂后期起始是必不可少的。Cdc20 的缺失导致侵袭性肿瘤的有效消退，而目前的有丝分裂药物显示出有限的效果。然而，Cdc20 缺失的细胞可以在 Cdk1 和激酶 Mastl（长城）失活后退出有丝分裂。这种有丝分裂的退出取决于含有 B55α 或 B55δ 调节亚基的 PP2A 磷酸酶复合物的活性。这些数据说明了哺乳动物中关键的有丝分裂后期退出的参与者的相关性，以及它们在肿瘤细胞中细胞死亡和有丝分裂后期退出之间的平衡中的意义。
