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. 2018 Feb;25(2):157-163.
doi: 10.1111/iju.13486. Epub 2017 Nov 8.

Astrocyte Elevated gene-1 Promotes Invasion and Epithelial-Mesenchymal Transition in Bladder Cancer Cells Through Activation of Signal Transducer and Activator of Transcription 3

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Astrocyte Elevated gene-1 Promotes Invasion and Epithelial-Mesenchymal Transition in Bladder Cancer Cells Through Activation of Signal Transducer and Activator of Transcription 3

Xiaoming Yang et al. Int J Urol. .
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Abstract

Objectives: To 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.

Methods: Gain- 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.

Results: Overexpression 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.

Conclusions: Astrocyte 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.

Keywords: astrocyte elevated gene-1; bladder cancer; epithelial-mesenchymal transition; growth; invasion; metastasis.

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