Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, GR 26504 Patras, Greece.
Recent Pat Anticancer Drug Discov. 2014 May;9(2):137-52. doi: 10.2174/1574892808666131119095953.
A large number of mostly recent reports show enhanced expression of the multi-functional protein nucleolin (NCL) on the surface of activated lymphocytes, angiogenic endothelial and many different types of cancer cells. Translocation of NCL at the external side of the plasma membrane occurs via a secretory pathway independent of the endoplasmic reticulum-Golgi complex, requires intracellular intact actin cytoskeleton, and seems to be mediated by a variety of factors. Cell surface NCL serves as a binding partner of several molecules implicated in cell differentiation, adhesion, and leukocyte trafficking, inflammation, angiogenesis and tumor development, mediating their biological activities and in some cases, leading to their internalization. Accumulating evidence validates cell surface NCL as a strategic target for treatment of cancer, while its property of tumor-specific uptake of targeted ligands seems to be useful for the development of non-invasive imaging tools for the diagnosis of cancer and for the targeted release of chemotherapeutic drugs. The observation that cell surface NCL exists in complexes with several other proteins implicated in tumorigenesis and angiogenesis suggests that targeting cell surface NCL might trigger multi-inhibitory effects, depending on the cell type. This review summarizes papers and patents related to the redistribution and the biological functions of cell surface NCL, with emphasis on the potential importance and advantages of developing efficient anti-cell surface NCL strategies.
大量的报告主要是最近的研究表明多功能蛋白核仁素（NCL）在激活的淋巴细胞、血管生成内皮细胞和许多不同类型的癌细胞表面表达增强。NCL 通过不依赖内质网-高尔基体复合物的分泌途径向质膜外侧易位，需要细胞内完整的肌动蛋白细胞骨架，并且似乎由多种因子介导。细胞表面 NCL 作为几种参与细胞分化、黏附和白细胞迁移、炎症、血管生成和肿瘤发展的分子的结合伴侣，调节其生物学活性，并在某些情况下导致其内化。越来越多的证据证实细胞表面 NCL 是治疗癌症的战略靶点，而其对靶向配体的肿瘤特异性摄取的特性似乎有助于开发用于癌症诊断的非侵入性成像工具和用于靶向释放化疗药物。观察到细胞表面 NCL 与几种其他参与肿瘤发生和血管生成的蛋白质存在复合物，表明针对细胞表面 NCL 可能会根据细胞类型触发多抑制作用。本文综述了与细胞表面 NCL 的重分布和生物学功能相关的论文和专利，重点介绍了开发有效抗细胞表面 NCL 策略的潜在重要性和优势。
