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


ABSTRACT: Galectin-1, a ?-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 overexpression 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-?B (NF-?B). Analysis of patient specimens confirmed the clinical significance and positive correlation between galectin-1 and CXCR4 expression levels and revealed concomitant overexpression 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-?B. 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.

SUBMITTER: Huang CS 

PROVIDER: S-EPMC4073433 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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

Huang Chang-Shuo CS   Tang Shye-Jye SJ   Chung Ling-Yen LY   Yu Cheng-Ping CP   Ho Jar-Yi JY   Cha Tai-Lung TL   Hsieh Chii-Cheng CC   Wang Hsiao-Hsien HH   Sun Guang-Huan GH   Sun Kuang-Hui KH  

Journal of the American Society of Nephrology : JASN 20140207 7


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 overexpression of galectin-1 in both kidney cancer cell lines and metastatic tissue specimens from patients with renal ce  ...[more]

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