Research Papers:
Sulfatase 1 (hSulf-1) reverses basic fibroblast growth factor-stimulated signaling and inhibits growth of hepatocellular carcinoma in animal model
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Abstract
Gaoya Xu1,2,*, Weidan Ji1,*, Yinghan Su3,*, Yang Xu1, Yan Yan1, Shuwen Shen1, Xiaoya Li1, Bin Sun1, Haihua Qian1, Lei Chen1, Xiaohui Fu1, Mengchao Wu1 and Changqing Su1,2
1 Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & National Center of Liver Cancer, The Second Military Medical University, Shanghai, China
2 Department of Pathogen Biology, School of Biology & Basic Medical Sciences, Soochow University, Suzhou, China
3 Department of Biology, Xi’an Jiaotong-Liverpool University, Suzhou, China
* These authors contributed equally to this work
Correspondence:
Changqing Su, email:
Keywords: human sulfatase 1; cell cycle; apoptosis; AKT/ERK signaling; hepatocellular carcinoma
Received: February 9, 2014 Accepted: June 6, 2014 Published: June 8, 2014
Abstract
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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PII: 2078