title: Aurora-A regulates autophagy through the Akt pathway in human prostate cancer.
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.
authors.forename: Shiying
authors.initials: S
authors.lastname: Zhang
authors.forename: Jianye
authors.initials: J
authors.lastname: Li
authors.forename: Gaobiao
authors.initials: G
authors.lastname: Zhou
authors.forename: Dawei
authors.initials: D
authors.lastname: Mu
authors.forename: Jingmin
authors.initials: J
authors.lastname: Yan
authors.forename: Jizhang
authors.initials: J
authors.lastname: Xing
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yao
authors.forename: Haibo
authors.initials: H
authors.lastname: Sheng
authors.forename: Di
authors.initials: D
authors.lastname: Li
authors.forename: Chao
authors.initials: C
authors.lastname: Lv
authors.forename: Bin
authors.initials: B
authors.lastname: Sun
authors.forename: Quan
authors.initials: Q
authors.lastname: Hong
authors.forename: Heqing
authors.initials: H
authors.lastname: Guo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D064096:Aurora Kinase A / Q000235:genetics*; D001343:Autophagy / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D051058:Oncogene Protein v-akt / Q000235:genetics; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
chemical_list: C576917:AURKA protein, human; D064096:Aurora Kinase A; D051058:Oncogene Protein v-akt
keywords: Aurora A; autophagy; chromosome instability gene; prostate cancer