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A core human primary tumor angiogenesis signature identifies the endothelial orphan receptor ELTD1 as a key regulator of angiogenesis

机译:核心人类原发性肿瘤血管生成特征将内皮孤儿受体ELTD1识别为血管生成的关键调节剂

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摘要

Limited clinical benefits derived from anti-VEGF therapy have driven the identification of new targets involved in tumor angiogenesis. Here, we report an integrative meta-analysis to define the transcriptional program underlying angiogenesis in human cancer. This approach identified ELTD1, an orphan G-protein-coupled receptor whose expression is induced by VEGF/bFGF and repressed by DLL4 signaling. Extensive analysis of multiple cancer types demonstrates significant upregulation of ELTD1 in tumor-associated endothelial cells, with a higher expression correlating with favorable prognosis. Importantly, ELTD1 silencing impairs endothelial sprouting and vessel formation invitro and invivo, drastically reducing tumor growth and greatly improving survival. Collectively, these results provide insight into the regulation of tumor angiogenesis and highlight ELTD1 as key player in blood vessel formation.
机译:从抗VEGF治疗获得的有限的临床益处已推动了与肿瘤血管生成有关的新靶标的鉴定。在这里,我们报告了整合的荟萃分析,以定义人类癌症中血管生成的基础转录程序。该方法鉴定了ELTD1,一种孤儿G蛋白偶联受体,其表达受VEGF / bFGF诱导并被DLL4信号传导抑制。对多种癌症类型的广泛分析表明,在肿瘤相关内皮细胞中ELTD1明显上调,且其表达较高与预后良好相关。重要的是,ELTD1沉默会在体内和体外损害内皮发芽和血管形成,从而大大减少肿瘤的生长并大大提高存活率。总的来说,这些结果提供了对肿瘤血管生成调控的见解,并突出了ELTD1作为血管形成的关键参与者。

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    《Cancer Cell》 |2013年第2期|共13页
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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 肿瘤学;
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