Affiliations: Department of Urology, Air Force General Hospital of PLA, Beijing 100142, China
Correspondence:
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Corresponding author: Heqing Guo, Department of Urology, Air Force General Hospital, 30 Fucheng road, Haidian distinct, Beijing 100142, China. Tel.: +86 010 66928392; Fax: +86 010 66927624; E-mail:[email protected]
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
