Molecular Oncology Laboratories, Department of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.
Biochem Soc Trans. 2011 Dec;39(6):1612-8. doi: 10.1042/BST20110721.
Notch signalling is a key pathway controlling angiogenesis in normal tissues and tumours. This has become a major focus of development of anticancer therapy, but to develop this appropriately, we need further understanding of the mechanisms of regulation of Dll4 (Delta-like ligand 4), a key endothelial Notch ligand. Dll4 and VEGF (vascular endothelial growth factor) cross-talk, with VEGF up-regulation of Dll4 and Dll4 down-regulating VEGFR (VEGF receptor) signalling. Both are essential for normal angiogenesis, and blockade of one may produce compensatory changes in the other. The present review considers recent developments in the regulation of Dll4 expression and functions, its role as a mechanism of resistance to anti-angiogenic therapy, and methods needed to develop effective therapy against this target.
Notch 信号通路是控制正常组织和肿瘤血管生成的关键途径。这已成为开发抗癌疗法的主要焦点，但为了适当地开发这种疗法，我们需要进一步了解 Dll4（Delta-like 配体 4）的调节机制，Dll4 是内皮 Notch 配体的关键。Dll4 和 VEGF（血管内皮生长因子）相互作用，VEGF 上调 Dll4，Dll4 下调 VEGFR（VEGF 受体）信号。两者对于正常的血管生成都是必不可少的，阻断其中一种可能会导致另一种产生代偿性变化。本综述考虑了 Dll4 表达和功能调节的最新进展，它作为抗血管生成治疗耐药机制的作用，以及开发针对该靶点的有效治疗方法所需的方法。
