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

被引：40

作者：

Ruan, Hailong ^{[1
]}

Yang, Hongmei ^{[2
]}

Wei, Haibin ^{[3
]}

Xiao, Wen ^{[1
]}

Lou, Ning ^{[1
]}

Qiu, Bin ^{[1
]}

Xu, Guanghua ^{[1
]}

Song, Zhengshuai ^{[1
]}

Xiao, Haibin ^{[1
]}

Liu, Lei ^{[1
]}

Zhou, Yali ^{[2
]}

Hu, Wenjun ^{[2
]}

Chen, Ke ^{[1
]}

Chen, Xuanyu ^{[3
,4
]}

Zhang, Xiaoping ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Union Hosp, Dept Urol, Tongji Med Coll, 1277 Jiefang Ave, Wuhan 430022, Hubei, Peoples R China

[2] Huazhong Univ Sci & Technol, Sch Basic Med, Dept Pathogen Biol, Wuhan 430030, Hubei, Peoples R China

[3] Zhejiang Prov Peoples Hosp, Dept Urol, 158 Shangtang Rd, Hangzhou 310014, Zhejiang, Peoples R China

[4] Augusta Univ, Dept Neurosci & Regenerat Med, Med Coll Georgia, Augusta, GA 30912 USA

来源：

INTERNATIONAL JOURNAL OF ONCOLOGY | 2017年 / 51卷 / 01期

基金：

中国国家自然科学基金; 国家高技术研究发展计划(863计划);

关键词：

SOX4; metastasis; epithelial-mesenchymal transition; AKT; p-AKT; renal cell carcinoma; PROSTATE-CANCER PROGRESSION; TRANSCRIPTION FACTORS; MASTER REGULATOR; EXPRESSION; METASTASIS; ACTIVATION; MELANOMA; TARGET; GENES; RESISTANCE;

D O I：

10.3892/ijo.2017.4010

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 TGF beta-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.

引用

页码：336 / 346

页数：11

共 46 条

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