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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis
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Aurora Kinases
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Carcinoma, Hepatocellular / metabolism
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Carcinoma, Hepatocellular / pathology
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Cell Line, Tumor
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Down-Regulation
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Forkhead Box Protein O1
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Forkhead Transcription Factors / antagonists & inhibitors
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / metabolism*
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G2 Phase Cell Cycle Checkpoints
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Hep G2 Cells
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Humans
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Liver Neoplasms / metabolism
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Liver Neoplasms / pathology
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M Phase Cell Cycle Checkpoints
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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RNA Interference
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RNA, Small Interfering / metabolism
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Tumor Suppressor Protein p53 / metabolism
Substances
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FOXO1 protein, human
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Forkhead Box Protein O1
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Forkhead Transcription Factors
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RNA, Small Interfering
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Tumor Suppressor Protein p53
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Aurora Kinases
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Protein Serine-Threonine Kinases