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

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.