IR@PKUHSC  > 北京大学第二临床医学院  > 外科肿瘤研究室
学科主题临床医学
HSulf-1 inhibits cell proliferation and invasion in human gastric cancer
Li, Jie1; Mo, Min-Li1; Chen, Zhao1; Yang, Jie1; Li, Qiu-Shi1; Wang, Dian-Jun2; Zhang, Hui3,4; Ye, Ying-Jiang3,4; Xu, Jun-Pu5; Li, Hai-Long6; Zhang, Fang6; Zhou, Hai-Meng1,6
刊名CANCER SCIENCE
2011-10-01
DOI10.1111/j.1349-7006.2011.02024.x
102期:10页:1815-1821
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]HEPARAN-SULFATE PROTEOGLYCANS ; HEPATOCELLULAR-CARCINOMA ; SIGNALING PATHWAY ; TUMOR-GROWTH ; IN-VIVO ; WNT ; PROMOTES ; CATENIN ; GASTRULATION ; ANGIOGENESIS
英文摘要

The HSulf-1 gene encodes an extracellular 6-O-endosulfatase and regulates the sulfation status of heparan sulfate proteoglycans (HSPG). We have demonstrated that promoter hypermethylation is correlated with the HSulf-1 silencing in gastric cancer. To investigate the functional importance of HSulf-1 silencing in gastric cancer, we restored HSulf-1 expression in the gastric cancer cell line MKN28, which lacks endogenous HSulf-1. Following restoration of expression, HSulf-1 inhibited cell proliferation, motility, and invasion in vitro, as well as significantly suppressing the MKN28 xenograft model (P < 0.05). No noticeable changes in proliferation and motility were observed following restoration of HSulf-1 in another gastric cancer cell line, namely AGS cells. Interestingly, in MKN28 cells, which have been reported to be dependent on extracellular Wnt signaling, we found that HSulf-1 inhibited the transcriptional activity of the Wnt/beta-catenin pathway and downregulated its targeted genes. Conversely, in AGS cells, in the constitutive Wnt/beta-catenin pathway is active, HSulf-1 had no effect on the activity of the Wnt/beta-catenin pathway. Furthermore, transfection of Wnt3a cDNA or beta-catenin shRNA resulted in rescue or enhancement, respectively, of the effects of HSulf-1 in MKN28 cells. Furthermore, HSPG epitope analysis confirmed that HSulf-1 affected the structure of heparan sulfate on the cell surface. Together, the results of the present study suggest that extracellular HSulf-1 may function as a negative regulator of proliferation and invasion in gastric cancer by suppressing Wnt/beta-catenin signaling at the cell surface. (Cancer Sci 2011; 102: 1815-1821)

语种英语
WOS记录号WOS:000304370600004
项目编号2007CB914401 ; 2011CB910803 ; 30770475
资助机构National Key Basic Research Project ; National Key Basic Research and Development (973) Program of China ; China Natural Science Foundation ; Beijing ACCB Biotech
引用统计
被引频次:15[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54375
专题北京大学第二临床医学院_外科肿瘤研究室
作者单位1.Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China
2.Chinese Peoples Liberat Army Gen Hosp, Dept Pathol, Beijing, Peoples R China
3.Peking Univ Peoples Hosp, Surg Oncol Lab, Beijing, Peoples R China
4.Peking Univ Peoples Hosp, Dept Surg Gastroenterol, Beijing, Peoples R China
5.Beijing ACCB Biotech Ltd, Beijing, Peoples R China
6.Tsinghua Univ, Yangtze Delta Reg Inst, Zhejiang Prov Key Lab Appl Enzymol, Jiaxing, Zhejiang, Peoples R China
推荐引用方式
GB/T 7714
Li, Jie,Mo, Min-Li,Chen, Zhao,et al. HSulf-1 inhibits cell proliferation and invasion in human gastric cancer[J]. CANCER SCIENCE,2011,102(10):1815-1821.
APA Li, Jie.,Mo, Min-Li.,Chen, Zhao.,Yang, Jie.,Li, Qiu-Shi.,...&Zhou, Hai-Meng.(2011).HSulf-1 inhibits cell proliferation and invasion in human gastric cancer.CANCER SCIENCE,102(10),1815-1821.
MLA Li, Jie,et al."HSulf-1 inhibits cell proliferation and invasion in human gastric cancer".CANCER SCIENCE 102.10(2011):1815-1821.
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