Overexpression of SOX4 promotes cell migration and invasion of renal cell carcinoma by inducing epithelial-mesenchymal transition

Ruan,Hailong; Yang,Hongmei; Wei,Haibin; Xiao,Wen; Lou,Ning; Qiu,Bin; Xu,Guanghua; Song,Zhengshuai; Xiao,Haibin; Liu,Lei; Zhou,Yali; Hu,Wenjun; Chen,Ke; Chen,Xuanyu; Zhang,Xiaoping

doi:10.3892/ijo.2017.4010

Overexpression of SOX4 promotes cell migration and invasion of renal cell carcinoma by inducing epithelial-mesenchymal transition

Authors:
- Hailong Ruan
- Hongmei Yang
- Haibin Wei
- Wen Xiao
- Ning Lou
- Bin Qiu
- Guanghua Xu
- Zhengshuai Song
- Haibin Xiao
- Lei Liu
- Yali Zhou
- Wenjun Hu
- Ke Chen
- Xuanyu Chen
- Xiaoping Zhang
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Affiliations: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China, Department of Pathogenic Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Urology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China
Published online on: May 17, 2017 https://doi.org/10.3892/ijo.2017.4010
Pages: 336-346

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Abstract

Incomplete understanding remains in the molecular mechanisms underlying progression and metastasis of renal cancer. The transcription factor SOX4 is upregulated in various human malignancies, including renal cancer, indicating it may be involved in renal tumorigenesis. In this study, we explored this hypothesis by loss-of-function and gain-of-function assays of SOX4 in renal cancer cell lines and renal epithelial cell line. We found that specific knockdown of SOX4 in renal cancer cell lines significantly suppressed the migration and invasion of cancer cells; specific overexpression of SOX4 in renal epithelial cell line markedly promoted the migration and invasion of the cell line. Epithelial-mesenchymal transition (EMT), a fundamental morphogenesis process, is implicated in renal cancer progression and metastasis. Our results demonstrated that SOX4 positively regulated the expression of mesenchymal cell markers and negatively regulated the expression of epithelial cell marker, and was involved in signal transduction pathway of TGFβ-induced EMT. In addition, SOX4 induced EMT probably through modulating the AKT/p-AKT signaling cascade. Finally, we found that SOX4 was significantly upregulated in clinical renal cancer samples compared with corresponding normal tissues and associated with EMT process in clinical samples. Taken together, our findings confirm a crucial function of SOX4 in the metastasis of renal cancer through orchestrating EMT and establish that the function suppression of SOX4-AKT-EMT axis might be an attractive therapeutic intervention during renal cancer metastasis.

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