Decreased Selenium-Binding Protein 1 Enhances Glutathione Peroxidase 1 Activity and Downregulates HIF-1 to Promote Hepatocellular Carcinoma Invasiveness

Liver Cancer Institute, Fudan University, Shanghai, China.
Clinical Cancer Research (Impact Factor: 8.72). 04/2012; 18(11):3042-53. DOI: 10.1158/1078-0432.CCR-12-0183
Source: PubMed


We aimed to characterize the role of selenium-binding protein 1 (SBP1) in hepatocellular carcinoma (HCC) invasiveness and underlying clinical significance.
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-1α (HIF-1α) 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.
Decreased expression of SBP1 could promote tumor invasiveness by increasing GPX1 activity and diminishing HIF-1α expression in HCC; SBP1 could be a novel biomarker for predicting prognosis and guiding personalized therapeutic strategies, especially in patients with advanced HCC.

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Available from: Tadashi Kondo
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    • "Immunostain was scored using a 4-point scale (0–4) system according to the intensity of staining and the percentage of positive cells. IHC evaluation was performed according to the method described before [21]. For each case, 1000 cells were randomly selected and scored. "
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    • "In hepatocellular carcinoma (HCC), selenium-binding protein 1 (SBP1) and GPX1 formed nuclear bodies and colocalized under oxidative stress. A decrease of SBP1 was linked with increased GPX1 activity, and it correlated with vascular invasion and a poor outcome [21]. GPX1 expression in different locations of tumor cells may have a different impact on tumor development, which warrants further investigation. "
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