极光激酶 A 的耗竭导致 FoxO1 的上调，从而诱导肝癌细胞的细胞周期停滞。
Depletion of Aurora A leads to upregulation of FoxO1 to induce cell cycle arrest in hepatocellular carcinoma cells.
机构信息
Biomedical Research Center Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea.
出版信息
Cell Cycle. 2013 Jan 1;12(1):67-75. doi: 10.4161/cc.22962.
Abstract
Aurora A kinase has drawn considerable attention as a therapeutic target for cancer therapy. However, the underlying molecular and cellular mechanisms of the anticancer effects of Aurora A kinase inhibition are still not fully understood. Herein, we show that depletion of Aurora A kinase by RNA interference (RNAi) in hepatocellular carcinoma (HCC) cells upregulated FoxO1 in a p53-dependent manner, which induces cell cycle arrest. Introduction of an RNAi-resistant Aurora A kinase into Aurora A-knockdown cells resulted in downregulation of FoxO1 expression and rescued proliferation. In addition, silencing of FoxO1 in Aurora A-knockdown cells allowed the cells to exit cytostatic arrest, which, in turn, led to massive cell death. Our results suggest that FoxO1 is responsible for growth arrest at the G2/M phase that is induced by Aurora A kinase inhibition.
摘要
极光激酶 A 作为癌症治疗的一个治疗靶点引起了相当大的关注。然而，极光激酶 A 抑制的抗癌作用的潜在分子和细胞机制仍不完全清楚。在此，我们表明 RNA 干扰 (RNAi) 敲低肝癌 (HCC) 细胞中的极光激酶 A 以依赖 p53 的方式上调 FoxO1，从而诱导细胞周期停滞。将 RNAi 抗性极光激酶 A 导入极光激酶 A 敲低细胞中会导致 FoxO1 表达下调并挽救增殖。此外，在极光激酶 A 敲低细胞中沉默 FoxO1 允许细胞退出细胞静止性抑制，这反过来又导致大量细胞死亡。我们的结果表明，FoxO1 负责由极光激酶 A 抑制诱导的 G2/M 期的生长停滞。
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1
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Int J Cancer. 2012 Dec 1;131(11):2693-703. doi: 10.1002/ijc.27579. Epub 2012 Jun 28.
2
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Cell Cycle. 2012 Feb 15;11(4):721-9. doi: 10.4161/cc.11.4.19171.
3
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Cell Cycle. 2012 Feb 15;11(4):807-17. doi: 10.4161/cc.11.4.19323.
4
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Oncotarget. 2011 Aug;2(8):599-609. doi: 10.18632/oncotarget.311.
5
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6
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Clin Cancer Res. 2010 Jun 15;16(12):3171-81. doi: 10.1158/1078-0432.CCR-09-3171. Epub 2010 Apr 27.
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8
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Mol Cancer Ther. 2010 Feb;9(2):268-78. doi: 10.1158/1535-7163.MCT-09-0765. Epub 2010 Feb 2.
9
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BJU Int. 2010 Jul;106(1):121-7. doi: 10.1111/j.1464-410X.2009.09047.x. Epub 2009 Nov 12.
10
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