Lethality to human cancer cells through massive chromosome loss by inhibition of the mitotic checkpoint
Lethality to human cancer cells through massive chromosome loss by inhibition of the mitotic checkpoint
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DOI：
10.1073/pnas.0401142101
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发表时间：
2004-06-08
影响因子：
11.1
通讯作者：
Cleveland, DW
中科院分区：
文献类型：
--
作者：
Kops, GJPL;Foltz, DR;Cleveland, DW
有丝分裂检查点是确保每个新细胞获得每条染色体的一个拷贝的主要机制，它被认为是致癌的一个因素。然而，检查点反应对细胞存活至关重要，包括染色体不稳定的结直肠癌细胞。降低人类癌细胞中检查点蛋白BubR1或Mad2的水平或抑制BubR1激酶活性会在六次分裂中引起凋亡细胞死亡，除非细胞分裂也被抑制。因此，有丝分裂检查点信号的抑制总是致命的，这是大量染色体丢失的结果，这一发现对抑制肿瘤细胞的增殖具有重要意义。
A compromised mitotic checkpoint, the primary mechanism for ensuring that each new cell receives one copy of every chromosome, has been implicated as a contributor to carcinogenesis. However, a checkpoint response is shown here to be essential for cell survival, including that of chromosomally instable colorectal cancer cells. Reducing the levels of the checkpoint proteins BubR1 or Mad2 in human cancer cells or inhibiting BubR1 kinase activity provokes apoptotic cell death within six divisions except when cytokinesis is also inhibited. Thus, suppression of mitotic checkpoint signaling is invariably lethal as the consequence of massive chromosome loss, findings that have implications for inhibiting proliferation of tumor cells.