Fez1/Lzts1 absence impairs Cdk1/Cdc25C interaction during mitosis and predisposes mice to cancer development
Fez1/Lzts1 absence impairs Cdk1/Cdc25C interaction during mitosis and predisposes mice to cancer development
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DOI：
10.1016/j.ccr.2007.01.014
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发表时间：
2007-03-01
期刊：
影响因子：
50.3
通讯作者：
Croce, Carlo M.
中科院分区：
文献类型：
--
作者：
Vecchione, Andrea;Baldassarre, Gustavo;Croce, Carlo M.
FEZ1/LZTS1 (LZTS1) 蛋白在不同组织类型的人类癌症中经常下调。 LZTS1 在正常组织中表达，由于 G2/M 期细胞的积累，将其引入癌细胞中可抑制细胞生长并抑制致瘤性。在这里，我们通过生成 Lzts1 敲除小鼠来定义其在细胞周期调节和肿瘤进展中的作用。在 Lzts1(-/-) 小鼠胚胎成纤维细胞 (MEF) 中，M 期 Cdc25C 降解增加，导致 Cdk1 活性降低。结果，Lzts1(-/-) MEF 显示出加速的有丝分裂进展、对紫杉醇和诺考达唑诱导的 M 期停滞的抗性以及不正确的染色体分离。因此，Lzts1 缺陷与小鼠自发性癌症和致癌物诱发癌症的发病率增加有关。
The FEZ1/LZTS1 (LZTS1) protein is frequently downregulated in human cancers of different histo-types. LZTS1 is expressed in normal tissues, and its introduction in cancer cells inhibits cell growth and suppresses tumorigenicity, owing to an accumulation of cells in G2/M. Here, we define its role in cell cycle regulation and tumor progression by generating Lzts1 knockout mice. In Lzts1(-/-) mouse embryo fibroblasts (MEFs), Cdc25C degradation was increased during M phase, resulting in decreased Cdk1 activity. As a consequence, Lzts1(-/-) MEFs showed accelerated mitotic progression, resistance to taxol- and nocodazole-induced M phase arrest, and improper chromosome segregation. Accordingly, Lzts1 deficiency was associated with an increased incidence of both spontaneous and carcinogen-induced cancers in mice.