Decreased selenium-binding protein 1 enhances glutathione peroxidase 1 activity and downregulates hif-1î± to promote hepatocellular carcinoma invasiveness Full Text
Clinical Cancer Research, 05/11/2012
Huang C et al. – Decreased expression of SBP1 could promote tumor invasiveness by increasing GPX1 activity and diminishing HIF-1alpha expression in HCC; SBP1 could be a novel biomarker for predicting prognosis and guiding personalized therapeutic strategies, especially in patients with advanced HCC.Methods
- SBP1 expression was measured in stepwise metastatic HCC cell lines by Western blotting.
- The role of SBP1 in HCC was investigated using siRNA.
- Immunofluorescence analyses were used to detect the interaction between SBP1 and glutathione peroxidase 1 (GPX1).
- Nineteen fresh tumor tissues and 323 paraffin-embedded samples were used to validate in vitro findings and to detect the prognostic significance of SBP1, respectively.
- Inhibition of SBP1 effectively increased cell motility, promoted cell proliferation, and inhibited apoptosis only under oxidative stress; it also greatly enhanced GPX1 activity without altering GPX1 expression and downregulated hypoxia-inducible factor-1alpha (HIF-1alpha) expression.
- SBP1 and GPX1 formed nuclear bodies and colocalized under oxidative stress.
- In freshly isolated clinical HCC tissues, decreased SBP1 was linked with increased GPX1 activity and correlated with vascular invasion.
- Tumor tissue microarrays indicated that SBP1 was an independent risk factor for overall survival and disease recurrence; patients with lower SBP1 expression experienced shorter overall survival periods and higher rates of disease recurrence (P < 0.001).
- Further analyses indicated that the predictive power of SBP1 was more significant for patients beyond the Milan criteria than patients within the Milan criteria.