Nogo-B受体在恶性实体肿瘤发病中的抑制和促进作用

Nogo-B是网状蛋白家族4的重要成员，广泛表达于中枢神经系统及外周组织。研究显示，Nogo-B能与Nogo受体1（NgR1）、Nogo-B特异性受体（NgBR）和配对免疫球蛋白样受体B（PirB）3种不同的受体结合，受体通过RhoA/Rho相关蛋白激酶（ROCK）、磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/Akt）、磷酸腺苷活化激酶α/肝X受α（AMPAα/LXRα）、细胞外信号调节激酶（ERK）、上皮-间质转化（EMT）以及未折叠蛋白反应（UPR）等多个信号通路，在血管生成、增殖和凋亡以及侵袭和迁移等肿瘤发生和发展过程中发挥抑制和促进的双重作用。了解Nogo-B受体参与肿瘤发病的机制将会为治疗药物的开发提供新的思路。我们将对Nogo-B及其受体的基本结构和表达以及Nogo-B受体信号通路在恶性实体肿瘤发生和发展中的抑制和促进作用等方面的最新研究进展做一简要综述。

Suppressing and activating effects of Nogo-B receptors in the pathogenesis of malignant solid tumors

Nogo-B is a major family member of the reticulon protein family 4. It is widely expressed in the central nervous system and peripheral tissues. Studies have shown that Nogo-B binds to three different receptors: Nogo receptor-1 (NgR1), Nogo-B specific receptor(NgBR) and paired immunoglobulin like receptor B(PirB). These receptors play a dual role of suppression and promotion in angiogenesis, proliferation and apoptosis, invasion and migration, which are important events in tumor development and progression, through various post-receptor signaling pathways, including RhoA/Rho-associated coiled-coil contaning protein kinase(RhoA/ROCK), phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), adenosine 5-monophosphate-activated protein kinase α/liver X receptor α(AMPAα/LXRα), extracellular signal-regulated kinase(ERK), epithelial-mesenchymal transition(EMT), unfolded protein response(UPR) and so on. An in-depth understanding of the mechanisms by which Nogo-B receptors are involved in tumor pathogeneis will provide new insights into the development of drugs. Here, we will summarize the up-to-date researches on the basic structure and expression of Nogo-B/Nogo-B receptors and the suppressing/activating effects of post-receptor signaling pathways in the pathogenesis of malignant solid tumors.