Galectin-1 upregulates CXCR4 to promote tumor progression and poor outcome in kidney cancer

Chang Shuo Huang, Shye Jye Tang, Ling Yen Chung, Cheng Ping Yu, Jar Yi Ho, Tai Lung Cha, Chii Cheng Hsieh, Hsiao Hsien Wang, Guang Huan Sun*, Kuang Hui Sun

*此作品的通信作者

研究成果: Article同行評審

41 引文 斯高帕斯(Scopus)

摘要

Galectin-1, a β-galactoside-binding lectin, is involved in many physiologic and pathologic processes, including cell adhesion, differentiation, angiogenesis, and tumor progression. However, the role of galectin- 1 in kidney cancer remains elusive. This study evaluated the role of galectin-1 in the progression and clinical prognosis of renal cell carcinoma. We found significant over expression of galectin-1 in both kidney cancer cell lines and metastatic tissue specimens from patients with renal cell carcinoma. Knockdown of galectin-1 gene expression in renal cancer cell lines reduced cell invasion, clonogenic ability, and epithelial-mesenchymal transition in vitro; reduced tumor outgrowth in vivo; and inhibited the angiogenesis-inducing activity of these cells in vitro and in vivo. Galectin-1 knockdown decreased CXCR4 expression levels in kidney cancer cells, and restoration of CXCR4 expression in galectin-1-silenced cells rescued cell motility and clonogenic ability. Additional studies suggested that galectin-1 induced CXCR4 expression through activation of nuclear factor-κB (NF-κB). Analysis of patient specimens confirmed the clinical significance and positive correlation between galectin-1 and CXCR4 expression levels and revealed concomitant over expression of galectin-1 and CXCR4 associated adversely with overall and disease-free survival. Our findings suggest that galectin-1 promotes tumor progression through upregulation of CXCR4 via NF-κB. The coordinated upregulation of galectin-1 and CXCR4 may be a novel prognostic factor for survival in patients with renal cell carcinoma and the galectin-1-CXCR4 axis may serve as a therapeutic target in this disease.

原文English
頁(從 - 到)1486-1495
頁數10
期刊Journal of the American Society of Nephrology
25
發行號7
DOIs
出版狀態Published - 1 7月 2014

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