Invasive potential of hepatocellular carcinoma is enhanced by loss of selenium-binding protein 1 and subsequent upregulation of CXCR4

American Journal of Cancer Research

Ping-Ting Gao¹  Rui-Zhao Dong²  Xuan Yang³  Guang-Yu Ding⁴ 

[1] Department of Liver Surgery Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China;Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China;Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China;Key Laboratory for Carcinogenesis and Cancer Invasion, Chinese Ministry of Education, Shanghai, China

关键词: Selenium-binding protein 1;    CXCR4;    epithelial-mesenchymal transition;    hepatocellular carcinoma;   

DOI  :  

学科分类：肿瘤学

来源: e-Century Publishing Corporation

【 摘 要 】

Decreased selenium-binding protein 1 (SBP1) is associated with increased invasion and poor prognosis of hepatocellular carcinoma (HCC). However, the underlying mechanism remains unknown. To unravel this mechanism, HCC cells expressing SBP1 were constructed and the impact on migration, invasion, and epithelial-mesenchymal transition (EMT) was evaluated. SBP1 expression reduced HCC cell migration and invasion by inhibiting EMT. Gene expression profiles of control and SBP1 expressing HCC cells revealed 186 differentially expressed genes, of which fibroblast growth factor 5, vascular endothelial growth factor receptor 1, and C-X-C motif chemokine receptor 4 (CXCR4) showed the greatest differences. CXCR4 expression was inhibited by SBP1 and restored the migration and invasion ability of HCC cells through activation of AKT signaling. Tumor samples from 200 HCC patients supported our in vitro findings and revealed an inverse correlation between SBP1 and CXCR4 expression. Patients with low SBP1 and high CXCR4 expression had the poorest prognosis and survival rate. Our results suggest that downregulation of SBP1 induces increased CXCR4 expression and results in EMT of HCC cells. Together, SBP1 and CXCR4 are promising potential biomarkers and therapeutic targets for HCC patients.

【 授权许可】

CC BY-NC