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

• Published in: International journal of urology 2018-02, Vol.25 (2), p.157-163
• Main Authors: Yang, Xiaoming, Shi, Lei, Yi, Chengzhi, Yang, Yang, Chang, Liansheng, Song, Dongkui
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - metabolism; astrocyte elevated gene‐1; Bladder cancer; Cadherins - metabolism; Cancer; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Line, Tumor; Down-Regulation; E-cadherin; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; growth; Humans; invasion; Invasiveness; Lung Neoplasms - secondary; Male; Mesenchyme; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Nuclear Proteins - metabolism; Phosphorylation; Signal Transduction; STAT3 Transcription Factor - metabolism; Transcription activation; Tumors; Twist-Related Protein 1 - metabolism; Up-Regulation; Urinary bladder; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - pathology; Vimentin; Xenograft Model Antitumor Assays; Xenografts
• ISSN: 0919-8172; 1442-2042
• DOI: 10.1111/iju.13486

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.