Research Papers:

Sulfatase 1 (hSulf-1) reverses basic fibroblast growth factor-stimulated signaling and inhibits growth of hepatocellular carcinoma in animal model

Gaoya Xu, Weidan Ji, Yinghan Su, Yang Xu, Yan Yan, Shuwen Shen, Xiaoya Li, Bin Sun, Haihua Qian, Lei Chen, Xiaohui Fu, Mengchao Wu and Changqing Su _

PDF  |  HTML  |  How to cite

Oncotarget. 2014; 5:5029-5039. https://doi.org/10.18632/oncotarget.2078

Metrics: PDF 2183 views  |   HTML 2516 views  |   ?  


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


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


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.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 2078