AI Article Synopsis
- Aurora A kinase is a promising target for cancer treatment, but its exact mechanisms of action are not fully understood.
- In hepatocellular carcinoma (HCC) cells, reducing Aurora A kinase levels through RNA interference activates FoxO1, leading to cell cycle arrest in a way that depends on p53.
- Experiments showed that restoring Aurora A kinase levels reduces FoxO1 and allows cancer cells to proliferate, while silencing FoxO1 in these cells leads to significant cell death, indicating FoxO1's critical role in controlling growth during the G2/M phase when Aurora A kinase is inhibited.
Article 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.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570518 | PMC |
| http://dx.doi.org/10.4161/cc.22962 | DOI Listing |
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