Zhang Shiying, Li Jianye, Zhou Gaobiao, Mu Dawei, Yan Jingmin, Xing Jizhang, Yao Zhiyong, Sheng Haibo, Li Di, Lv Chao, Sun Bin, Hong Quan, Guo Heqing
Cancer Biomark. 2017;19(1):27-34. doi: 10.3233/CBM-160238.
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.
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.
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.
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.
极光激酶A（Aurora A kinase）在包括前列腺癌在内的多种肿瘤类型中经常过度表达。然而，Aurora A在前列腺癌自噬中的功能尚未得到研究。在此，我们旨在研究Aurora A在前列腺癌中的作用机制及与自噬相关的信号通路。
为研究Aurora A的生物学功能，进行Aurora A的下调，随后进行功能测试分析。采用免疫组织化学法检测人前列腺癌标本中Aurora A的表达。进行CCK8、Transwell、流式细胞术分析以及裸鼠肿瘤形成测量，以测试Aurora A下调在体内和体外的作用。通过蛋白质免疫印迹法进行信号通路分析。通过监测LC3-II的表达水平来测量自噬活性。
人前列腺癌标本中Aurora A的过表达明显高于良性前列腺增生（BPH）。此外，敲低Aurora A通过抑制Akt通路抑制前列腺癌细胞的增殖，表明Akt是前列腺癌中一种新的Aurora A底物。此外，下调Aurora A可促使前列腺癌细胞发生自噬。最重要的是，敲除Aurora A几乎完全消除了裸鼠体内的肿瘤发生，表明Aurora A是前列腺癌中的关键致癌效应因子。
综上所述，我们的数据表明，Aurora-A通过抑制Akt的磷酸化在抑制自噬中发挥重要作用，这反过来又阻止了前列腺癌中自噬诱导的细胞凋亡。
