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RKTG inhibits angiogenesis by suppressing MAPK-mediated autocrine VEGF signaling and is downregulated in clear-cell renal cell carcinoma
文献类型：期刊论文
| 作者 | Zhang, Y.; Jiang, X.; Qin, X.; Ye, D.; Yi, Z.; Liu, M.; Bai, O.; Liu, W.; Xie, X.; Wang, ZhenZhen（王甄真） |
| 刊名 | ONCOGENE
 |
| 出版日期 | 2010 |
| 卷号 | 29期号:39页码:5404-5415 |
| 关键词 | RKTG ccRCC angiogenesis VEGF HIF-1 alpha p300 |
| 通讯作者 | Chen, Y (reprint author), Chinese Acad Sci, Grad Sch, Key Lab Nutr & Metab, Inst Nutr Sci,Shanghai Inst Biol Sci, 294 Taiyuan Rd,Rm307, Shanghai 200031, Peoples R China. |
| 英文摘要 | Vascular endothelial growth factors (VEGFs) are crucial regulators of angiogenesis and vasculogenesis. The autocrine VEGF signaling is required for maintaining the homeostasis of vasculature. Dysregulation of angiogenesis is implicated in the development of many human cancers, especially in clear-cell renal cell carcinoma (ccRCC), a highly vascularized tumor. Meanwhile, antiangiogenesis has become a mainstay in the treatment of human cancers. In this study, we analyzed the functional roles of RKTG (Raf Kinase Trapping to Golgi), a negative regulator of mitogen-activated protein kinase (Raf/MEK/ERK) signaling, by sequestration of Raf kinase to the Golgi apparatus, in angiogenesis and ccRCC. Through a series of in vitro and in vivo experiments, we found that RKTG has a negative effect on cell proliferation, migration, sprouting and angiogenesis of endothelial cells. RKTG, by suppressing mitogen-activated protein kinase signaling, negatively regulates the transactivation activity of hypoxia-inducible factor 1 alpha (HIF-1 alpha) by inhibiting formation of HIF-1 alpha/p300 complex and suppressing VEGF transcription, thereby reducing hypoxia-induced VEGF production. The expression level of RKTG is significantly downregulated in clinical ccRCC tumor samples, with an inverse correlation with VEGF expression level. These results highlight the functional roles of RKTG and its regulated Raf/ERK/MEK signaling cascade in angiogenesis and autocrine VEGF signaling. In addition, this study indicates that RKTG is likely implicated in the development of ccRCC through its regulation on angiogenesis. Oncogene (2010) 29, 5404-5415; doi: 10.1038/onc.2010.270; published online 5 July 2010 |
| 类目[WOS] | Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity |
| 研究领域[WOS] | Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity |
| 关键词[WOS] | ENDOTHELIAL-GROWTH-FACTOR ; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA ; TUMOR-GROWTH ; FACTOR GENE ; PROTEIN ; RAF ; IDENTIFICATION ; PROLIFERATION ; TRANSDUCTION ; ACTIVATION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000282944500007 |
| 公开日期 | 2015-09-01 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/101]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_信号转导与营养相关疾病研究组 |
| 推荐引用方式 GB/T 7714 | Zhang, Y.,Jiang, X.,Qin, X.,et al. RKTG inhibits angiogenesis by suppressing MAPK-mediated autocrine VEGF signaling and is downregulated in clear-cell renal cell carcinoma[J]. ONCOGENE,2010,29(39):5404-5415. |
| APA | Zhang, Y..,Jiang, X..,Qin, X..,Ye, D..,Yi, Z..,...&Chen, Yan.(2010).RKTG inhibits angiogenesis by suppressing MAPK-mediated autocrine VEGF signaling and is downregulated in clear-cell renal cell carcinoma.ONCOGENE,29(39),5404-5415. |
| MLA | Zhang, Y.,et al."RKTG inhibits angiogenesis by suppressing MAPK-mediated autocrine VEGF signaling and is downregulated in clear-cell renal cell carcinoma".ONCOGENE 29.39(2010):5404-5415. |
入库方式： OAI收割
来源：上海营养与健康研究所
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