Bryostatin-5 Blocks Stromal Cell-Derived Factor-1 Induced Chemotaxis via Desensitization and Down-regulation of Cell Surface CXCR4 Receptors
文献类型：期刊论文
| 作者 | He, Xing1; Fang, Liyan1; Wang, Jue1; Yi, Yanghua2; Zhang, Shuyu2; Xie, Xin1
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| 刊名 | CANCER RESEARCH
 |
| 出版日期 | 2008-11-01 |
| 卷号 | 68期号:21页码:8678-8686 |
| ISSN号 | 0008-5472 |
| DOI | 10.1158/0008-5472.CAN-08-0294 |
| 文献子类 | Article |
| 英文摘要 | The chemokine receptor CXCR4 and its ligand, stromal cell-derived factor-1 (SDF-1), play important roles in hematopolesis regulation, lymphocyte activation, and trafficking, as well as in developmental processes, including organogenesis, vascularization, and embryogenesis. The receptor is also involved in HIV infection and tumor growth and metastasis. Antagonists of CXCR4 have been widely evaluated for drugs against HIV and tumors. In an effort to identify novel CXCR4 antagonists, we screened a small library of compounds derived from marine organisms and found bryostatin-5, which potently inhibits chemotaxis induced by SDF-1 in Jurkat cells. Bryostatin-5 is a member of the macrolactones, and its analogue bryostatin-1 is currently being evaluated in clinical trials for its chemotherapeutic potential. The involvement of bryostatins in the SDF-1/CXCR4 signaling process has never been reported. In this study, we found that bryostatin-5 potently inhibits SM-1-induced chemotaxis but does not affect serum-induced chemotaxis. Further studies indicate that this inhibitory effect is not due to receptor antagonism but rather to bryostatin-5-induced receptor desensitization and down-regulation of cell surface CXCR4. We also show that these effects are mediated by the activation of conventional protein kinase C. [Cancer Res 2008;68(21):8678-86] |
| WOS关键词 | PROTEIN-KINASE-C ; CHRONIC LYMPHOCYTIC-LEUKEMIA ; BREAST-CANCER ; HIV CORECEPTORS ; BETA-ARRESTINS ; METASTASIS ; EXPRESSION ; INTERNALIZATION ; PHOSPHORYLATION ; BONE |
| 资助项目 | National Natural Sciences Foundation of China[90713047] ; National Natural Sciences Foundation of China[30623008] ; Ministry of Science and Technology of China[2006AA020602] ; Chinese Academy of Sciences[KSCX2-Y1V-R-18] ; Shanghai Commission of Science and Technology[06DZ22907] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000260698900007 |
| 出版者 | AMER ASSOC CANCER RESEARCH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279446]  |
| 专题 | 国家新药筛选中心 |
| 通讯作者 | Xie, Xin |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Grad Univ, Natl Ctr Drug Screening,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China; 2.Second Mil Med Univ, Sch Pharm, Res Ctr Marine Drugs, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | He, Xing,Fang, Liyan,Wang, Jue,et al. Bryostatin-5 Blocks Stromal Cell-Derived Factor-1 Induced Chemotaxis via Desensitization and Down-regulation of Cell Surface CXCR4 Receptors[J]. CANCER RESEARCH,2008,68(21):8678-8686. |
| APA | He, Xing,Fang, Liyan,Wang, Jue,Yi, Yanghua,Zhang, Shuyu,&Xie, Xin.(2008).Bryostatin-5 Blocks Stromal Cell-Derived Factor-1 Induced Chemotaxis via Desensitization and Down-regulation of Cell Surface CXCR4 Receptors.CANCER RESEARCH,68(21),8678-8686. |
| MLA | He, Xing,et al."Bryostatin-5 Blocks Stromal Cell-Derived Factor-1 Induced Chemotaxis via Desensitization and Down-regulation of Cell Surface CXCR4 Receptors".CANCER RESEARCH 68.21(2008):8678-8686. |
入库方式： OAI收割
来源：上海药物研究所
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