Journal
ONCOTARGET
Volume 5, Issue 13, Pages 5029-5039Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.2078
Keywords
human sulfatase 1; cell cycle; apoptosis; AKT/ERK signaling; hepatocellular carcinoma
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Funding
- Plan Project of Shanghai Outstanding Academic Leaders [13XD1400300]
- National Significant Science and Technology Special Projects of New Drugs Creation [2014ZX09101003]
- National Significant Science and Technology Special Projects of Major Infectious Disease Prevention and Control [2013ZX10002008]
- National Natural Science Foundation of China [81370552, 81172303]
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The human sulfatase 1 (hSulf-1) gene encodes an endosulfatase that functions to inhibit the heparin-binding growth factor signaling, including the basic fibroblast growth factor (bFGF)-mediated pathway, by desulfating the cell surface heparan sulfate proteoglycans (HSPGs). bFGF could stimulate cell cycle progression and inhibit cell apoptosis, this biological effect can be reversed by hSulf-1. However, molecular mechanisms have not been fully reported. In the current study, by reactivation of hSulf-1 expression and function in the hSulf-1-negative hepatocellular carcinoma (HCC) cell lines and HCC xenograft tumors, we found that hSulf-1 blocked the bFGF effect on the promotion of cell cycle and inhibition of apoptosis. The bFGF-stimulated activation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) pathways was suppressed by hSulf-1, which led to a decreased expression of the target genes Cyclin D1 and Survivin, then finally induced cell cycle arrest and apoptosis in HCC cells. Our data suggested that hSulf-1 may be a suitable target for cancer therapy.
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