Astrocyte elevated gene-1 promotes invasion and epithelial-mesenchymal transition in bladder cancer cells through activation of signal transducer and activator of transcription 3

作者：Yang, Xiaoming; Shi, Lei; Yi, Chengzhi; Yang, Yang; Chang, Liansheng; Song, Dongkui^*

来源：International Journal of Urology, 2018, 25(2): 157-163.

DOI：10.1111/iju.13486

• astrocyte elevated gene-1
• bladder cancer
• epithelial-mesenchymal transition
• growth
• invasion
• metastasis

ObjectivesTo determine the impact of astrocyte elevated gene-1 on the invasion and epithelial-mesenchymal transition of bladder cancer cells in vitro and metastasis in vivo.
MethodsGain- and loss-of-function studies were carried out to investigate the biological roles of astrocyte elevated gene-1 in bladder cancer cell invasion, epithelial-mesenchymal transition and lung metastasis. The mechanism underlying the activity of astrocyte elevated gene-1 was examined.
ResultsOverexpression of astrocyte elevated gene-1 led to a significant increase in the invasive ability of UMUC3 and T24 bladder cancer cells in Matrigel invasion assays. In contrast, silencing of astrocyte elevated gene-1 restrained bladder cancer cell invasion. Overexpression of astrocyte elevated gene-1 downregulated E-cadherin and upregulated vimentin and Twist1, while silencing of astrocyte elevated gene-1 exerted an opposite effect. Mechanistically, astrocyte elevated gene-1 overexpression promoted the phosphorylation of signal transducer and activator of transcription 3 in bladder cancer cells. Treatment with WP1066, a specific signal transducer and activator of transcription 3 inhibitor, significantly abolished astrocyte elevated gene-1-induced invasion and epithelial-mesenchymal transition in UMUC3 cells. In vivo studies showed that astrocyte elevated gene-1 overexpression stimulated the growth of UMUC3 xenograft tumors and lung metastasis.
ConclusionsAstrocyte elevated gene-1 shows the ability to promote bladder cancer metastasis, which is causally linked to induction of signal transducer and activator of transcription 3 activation and epithelial-mesenchymal transition. Therefore, targeting astrocyte elevated gene-1 might offer therapeutic benefits in treating metastatic bladder cancer.

• 出版日期2018-2
• 单位郑州大学