Silencing of hHS6ST2 inhibits progression of pancreatic cancer through linhibition of Notch signalling
文献类型：期刊论文
| 作者 | Song, Kai3; Li, Qin3; Peng, Yong-Bo3; Li, Jie2; Ding, Kan2 ; Chen, Li-Juan1,6; Shao, Cheng-Hao5; Zhang, Li-Jun4; Li, Ping3
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| 刊名 | BIOCHEMICAL JOURNAL
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| 出版日期 | 2011-06-01 |
| 卷号 | 436页码:271-282 |
| 关键词 | angiogenesis epithelial-mesenchymal transition (EMT) heparan sulfate Notch pancreatic cancer proteomics 6-O-sulfotransferase |
| ISSN号 | 0264-6021 |
| DOI | 10.1042/BJ20110297 |
| 文献子类 | Article |
| 英文摘要 | Many of the ligands involved in developmental processes require HS (heparan sulfate) to modulate signal transduction. hHS6ST2 (human heparan sulfate D-glucosaminyl 6-O-sulfotransferase-2) is a Golgi-resident enzyme that usually acts on G1cA/IdoA(2S)-G1cNAc/NS disaccharide-6-sulfate modifications within the HS sequence. Emerging evidence indicates the importance of 6-O-sulfation in a number of developmental processes. However, any correlation with cancer-related events remains largely unexplored. In the present study, we found that hHS6ST2, but not other variants, was activated in human PC (pancreatic cancer). shRNA (short hairpin RNA)-mediated silencing of endogenous hHS6ST2 expression in the PC cell line PANC-1 inhibited cell invasion and migration. hHS6ST2 knockdown also resulted in markedly reduced tumorigenesis in immunocompromised mice. To specifically explore the molecular alterations resulting from depletion of hHS6ST2-generated 6-O-sulfation, we employed two-dimensional gel electrophoresis technology followed by nano-HPLC-ESI (electrospray ionization)-tandem MS to separate and identify total proteins from PC cells. Our data suggest that hHS6ST2 potentiates Notch signalling in PC cells. We also identified a role for hHS6ST2 in the growth and tumorigenicity of these cells which, at least in part, acts through Notch-mediated EMT (epithelial-mesenchymal transition) and angiogenesis. The results of the present study suggest that hHS6ST2 could be an attractive target for PC therapy. |
| WOS关键词 | EPITHELIAL-MESENCHYMAL TRANSITION ; HEPARAN-SULFATE 6-O-SULFOTRANSFERASE ; NONPRODUCTIVE ANGIOGENESIS ; VASCULAR DEVELOPMENT ; EXPRESSION ; CELLS ; ZEBRAFISH ; GROWTH ; BIOSYNTHESIS ; ACTIVATION |
| 资助项目 | Program for Changjiang Scholars and Innovative Research Team in University[IRT0868] ; National Science and Technology Major Project 'Creation of Major New Drugs' from China[2009ZX09502-020] ; National Science and Technology Major Project 'Creation of Major New Drugs' from China[2009ZX09301-001] ; National Science and Technology Major Project 'Creation of Major New Drugs' from China[2009ZX09103-071] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000291413200008 |
| 出版者 | PORTLAND PRESS LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278512]  |
| 专题 | 药理学第三研究室 |
| 通讯作者 | Li, Ping |
| 作者单位 | 1.Sichuan Univ, W China Hosp, W China Med Sch, State Key Lab Biotherapy, Chengdu 610064, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Glycochem & Glycobiol Lab, Shanghai 200031, Peoples R China; 3.China Pharmaceut Univ, Minist Educ, Key Lab Modern Chinese Med, Nanjing 210009, Peoples R China; 4.Shanghai Publ Hlth Clin Ctr, Shanghai, Peoples R China 5.Changhai Hosp, Dept Gen Surg, Shanghai, Peoples R China; 6.Sichuan Univ, W China Hosp, W China Med Sch, Ctr Canc, Chengdu 610064, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Song, Kai,Li, Qin,Peng, Yong-Bo,et al. Silencing of hHS6ST2 inhibits progression of pancreatic cancer through linhibition of Notch signalling[J]. BIOCHEMICAL JOURNAL,2011,436:271-282. |
| APA | Song, Kai.,Li, Qin.,Peng, Yong-Bo.,Li, Jie.,Ding, Kan.,...&Li, Ping.(2011).Silencing of hHS6ST2 inhibits progression of pancreatic cancer through linhibition of Notch signalling.BIOCHEMICAL JOURNAL,436,271-282. |
| MLA | Song, Kai,et al."Silencing of hHS6ST2 inhibits progression of pancreatic cancer through linhibition of Notch signalling".BIOCHEMICAL JOURNAL 436(2011):271-282. |
入库方式： OAI收割
来源：上海药物研究所
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