Angiogenesis Group, Institute for Biomedical Research, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Biochem Soc Trans. 2011 Dec;39(6):1571-5. doi: 10.1042/BST20110746.
We have in recent years described several endothelial-specific genes that mediate cell migration. These include Robo4 (roundabout 4), CLEC14A (C-type lectin 14A) and ECSCR (endothelial cell-specific chemotaxis regulator) [formerly known as ECSM2 (endothelial cell-specific molecule 2)]. Loss of laminar shear stress induces Robo4 and CLEC14A expression and an endothelial 'tip cell' phenotype. Low shear stress is found not only at sites of vascular occlusion such as thrombosis and embolism, but also in the poorly structured vessels that populate solid tumours. The latter probably accounts for strong expression of Robo4 and CLEC14A on tumour vessels. The function of Robo4 has, in the past, aroused controversy. However, the recent identification of Unc5B as a Robo4 ligand has increased our understanding and we hypothesize that Robo4 function is context-dependent. ECSCR is another endothelial-specific protein that promotes filopodia formation and migration, but, in this case, expression is independent of shear stress. We discuss recent papers describing ECSCR, including intracellular signalling pathways, and briefly contrast these with signalling by Robo4.
近年来，我们描述了几种介导细胞迁移的内皮特异性基因。这些基因包括 Robo4（roundabout 4）、CLEC14A（C 型凝集素 14A）和 ECSCR（内皮细胞特异性趋化调节因子）[以前称为 ECSM2（内皮细胞特异性分子 2）]。层流剪切应力的丧失诱导 Robo4 和 CLEC14A 的表达，并使内皮细胞呈现“尖端细胞”表型。低剪切应力不仅存在于血管阻塞部位，如血栓和栓塞，也存在于实体瘤中结构不良的血管中。后者可能是肿瘤血管中 Robo4 和 CLEC14A 强表达的原因。Robo4 的功能过去曾引起争议。然而，最近发现 Unc5B 是 Robo4 的配体，这增加了我们的理解，我们假设 Robo4 的功能是依赖于上下文的。ECSCR 是另一种促进丝状伪足形成和迁移的内皮特异性蛋白，但在这种情况下，其表达不依赖于剪切应力。我们讨论了最近描述 ECSCR 的论文，包括细胞内信号通路，并简要对比了 Robo4 的信号通路。
