Cargando…
Sulfatase 1 (hSulf-1) reverses basic fibroblast growth factor-stimulated signaling and inhibits growth of hepatocellular carcinoma in animal model
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...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148119/ https://www.ncbi.nlm.nih.gov/pubmed/24970807 |
_version_ | 1782332559013707776 |
---|---|
author | Xu, Gaoya Ji, Weidan Su, Yinghan Xu, Yang Yan, Yan Shen, Shuwen Li, Xiaoya Sun, Bin Qian, Haihua Chen, Lei Fu, Xiaohui Wu, Mengchao Su, Changqing |
author_facet | Xu, Gaoya Ji, Weidan Su, Yinghan Xu, Yang Yan, Yan Shen, Shuwen Li, Xiaoya Sun, Bin Qian, Haihua Chen, Lei Fu, Xiaohui Wu, Mengchao Su, Changqing |
author_sort | Xu, Gaoya |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4148119 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-41481192014-08-29 Sulfatase 1 (hSulf-1) reverses basic fibroblast growth factor-stimulated signaling and inhibits growth of hepatocellular carcinoma in animal model Xu, Gaoya Ji, Weidan Su, Yinghan Xu, Yang Yan, Yan Shen, Shuwen Li, Xiaoya Sun, Bin Qian, Haihua Chen, Lei Fu, Xiaohui Wu, Mengchao Su, Changqing Oncotarget Research Paper 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. Impact Journals LLC 2014-06-08 /pmc/articles/PMC4148119/ /pubmed/24970807 Text en Copyright: © 2014 Xu et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Xu, Gaoya Ji, Weidan Su, Yinghan Xu, Yang Yan, Yan Shen, Shuwen Li, Xiaoya Sun, Bin Qian, Haihua Chen, Lei Fu, Xiaohui Wu, Mengchao Su, Changqing Sulfatase 1 (hSulf-1) reverses basic fibroblast growth factor-stimulated signaling and inhibits growth of hepatocellular carcinoma in animal model |
title | Sulfatase 1 (hSulf-1) reverses basic fibroblast growth factor-stimulated signaling and inhibits growth of hepatocellular carcinoma in animal model |
title_full | Sulfatase 1 (hSulf-1) reverses basic fibroblast growth factor-stimulated signaling and inhibits growth of hepatocellular carcinoma in animal model |
title_fullStr | Sulfatase 1 (hSulf-1) reverses basic fibroblast growth factor-stimulated signaling and inhibits growth of hepatocellular carcinoma in animal model |
title_full_unstemmed | Sulfatase 1 (hSulf-1) reverses basic fibroblast growth factor-stimulated signaling and inhibits growth of hepatocellular carcinoma in animal model |
title_short | Sulfatase 1 (hSulf-1) reverses basic fibroblast growth factor-stimulated signaling and inhibits growth of hepatocellular carcinoma in animal model |
title_sort | sulfatase 1 (hsulf-1) reverses basic fibroblast growth factor-stimulated signaling and inhibits growth of hepatocellular carcinoma in animal model |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148119/ https://www.ncbi.nlm.nih.gov/pubmed/24970807 |
work_keys_str_mv | AT xugaoya sulfatase1hsulf1reversesbasicfibroblastgrowthfactorstimulatedsignalingandinhibitsgrowthofhepatocellularcarcinomainanimalmodel AT jiweidan sulfatase1hsulf1reversesbasicfibroblastgrowthfactorstimulatedsignalingandinhibitsgrowthofhepatocellularcarcinomainanimalmodel AT suyinghan sulfatase1hsulf1reversesbasicfibroblastgrowthfactorstimulatedsignalingandinhibitsgrowthofhepatocellularcarcinomainanimalmodel AT xuyang sulfatase1hsulf1reversesbasicfibroblastgrowthfactorstimulatedsignalingandinhibitsgrowthofhepatocellularcarcinomainanimalmodel AT yanyan sulfatase1hsulf1reversesbasicfibroblastgrowthfactorstimulatedsignalingandinhibitsgrowthofhepatocellularcarcinomainanimalmodel AT shenshuwen sulfatase1hsulf1reversesbasicfibroblastgrowthfactorstimulatedsignalingandinhibitsgrowthofhepatocellularcarcinomainanimalmodel AT lixiaoya sulfatase1hsulf1reversesbasicfibroblastgrowthfactorstimulatedsignalingandinhibitsgrowthofhepatocellularcarcinomainanimalmodel AT sunbin sulfatase1hsulf1reversesbasicfibroblastgrowthfactorstimulatedsignalingandinhibitsgrowthofhepatocellularcarcinomainanimalmodel AT qianhaihua sulfatase1hsulf1reversesbasicfibroblastgrowthfactorstimulatedsignalingandinhibitsgrowthofhepatocellularcarcinomainanimalmodel AT chenlei sulfatase1hsulf1reversesbasicfibroblastgrowthfactorstimulatedsignalingandinhibitsgrowthofhepatocellularcarcinomainanimalmodel AT fuxiaohui sulfatase1hsulf1reversesbasicfibroblastgrowthfactorstimulatedsignalingandinhibitsgrowthofhepatocellularcarcinomainanimalmodel AT wumengchao sulfatase1hsulf1reversesbasicfibroblastgrowthfactorstimulatedsignalingandinhibitsgrowthofhepatocellularcarcinomainanimalmodel AT suchangqing sulfatase1hsulf1reversesbasicfibroblastgrowthfactorstimulatedsignalingandinhibitsgrowthofhepatocellularcarcinomainanimalmodel |