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. 2017 May 6;19(1):27–34. doi: 10.3233/CBM-160238

Aurora-A regulates autophagy through the Akt pathway in human prostate cancer

Shiying Zhang 1, Jianye Li 1, Gaobiao Zhou 1, Dawei Mu 1, Jingmin Yan 1, Jizhang Xing 1, Zhiyong Yao 1, Haibo Sheng 1, Di Li 1, Chao Lv 1, Bin Sun 1, Quan Hong 1, Heqing Guo 1,*
PMCID: PMC13020708  PMID: 28269749

Abstract

BACKGROUND:

Aurora A kinase is frequently overexpressed in a variety of tumor types, including the prostate. However, the function of Aurora A in autophagy in prostate cancer has not been investigated. Here, we aimed to study the functioning mechanism and autophagy associated signaling pathways of Aurora A in prostate cancer.

METHODS:

To investigate the biological function of Aurora A, down-regulation of Aurora A was performed followed by functional testing assays. Immunohistochemistry was used to detect the expression of Aurora A in human prostate cancer specimens. CCK8, Transwell, flow cytometric analysis and measurement of tumor formation in nude mice were performed to test the effects of Aurora A down-regulation in vivo and in vitro. Signaling pathway analysis was performed by using Western blot. Autophagy activity was measured by monitoring the expression levels of LC3-II.

RESULTS:

Aurora A overexpression was significantly higher in human prostate cancer specimens than in BPH. Furthermore, Aurora A knockdown inhibited the proliferation of prostate cancer cells by suppressing the Akt pathway, indicating that Akt is a novel Aurora A substrate in prostate cancer. Additionally, Aurora A down-regulation prompts autophagy in prostate cancer cells. Most importantly, Aurora A ablation almost fully abrogates tumorigenesis in nude mice, suggesting that Aurora A is a key oncogenic effector in prostate cancer.

CONCLUSIONS:

Taken together, our data suggest that Aurora-A plays an important role in the suppression of autophagy by inhibiting the phosphorylation of Akt, which in turn prevents autophagy-induced apoptosis in prostate cancer.

Keywords: Aurora A, autophagy, prostate cancer, chromosome instability gene

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