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RKTG inhibits angiogenesis by suppressing MAPK-mediated autocrine VEGF signaling and is downregulated in clear-cell renal cell carcinoma 期刊论文

编号：

7a0899ea-e053-49d4-b6b8-20e64845fb5e
作者：

Zhang, Y.(张怡轩)#^[1]Jiang, X.#^[1]Qin, X.^[2];Ye, D.^[2];Yi, Z.^[3,4];Liu, M.^[3,4];Bai, O.(白鸥)^[5]Liu, W.^[1];Xie, X.^[1];Wang, Z.^[1];Fang, J.^[1];Chen, Y.(陈雁)*^[1]
语种：

English
期刊：

ONCOGENE ISSN：0950-9232 2010 年 29 卷 39 期 (5404 - 5415) ; SEP
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关键词：

RKTG ccRCC angiogenesis VEGF HIF-1 alpha p300
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
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.,&Chen Y..(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.
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