Department of Neurosurgery , Baylor Scott & White Health , Temple , Texas 78508 , United States.
Neuroscience Institute , Baylor Scott & White Health , Temple , Texas 76502 , United States.
J Am Chem Soc. 2019 Feb 27;141(8):3613-3622. doi: 10.1021/jacs.8b12872. Epub 2019 Feb 13.
The aim of this study is to illuminate a novel therapeutic approach by identifying a functional binding target of salinomycin, an emerging anticancer stem cell (CSC) agent, and to help dissect the underlying action mechanisms. By utilizing integrated strategies, we identify that nucleolin (NCL) is likely a salinomycin-binding target and a critical regulator involved in human neuroblastoma (NB) CSC activity. Salinomycin markedly suppresses NB CD34 expression and reduces CD34+ cell population in an NCL-dependent manner via disruption of the interaction of NCL with CD34 promoter. The elevated levels of NCL expression in NB tumors are associated with poor patient survival. Altogether, these results indicate that NCL is likely a novel functional salinomycin-binding target that exhibits the potential to be a prognostic marker for NB therapy.
本研究旨在通过鉴定新型抗癌干细胞(CSC)药物盐霉素的功能结合靶点,阐明一种新的治疗方法,并帮助剖析其潜在作用机制。通过综合运用多种策略,我们发现核仁素(NCL)可能是盐霉素的结合靶标和关键调控因子,参与人神经母细胞瘤(NB)CSC 活性。盐霉素通过破坏 NCL 与 CD34 启动子的相互作用,显著抑制 NB CD34 的表达,并以 NCL 依赖的方式减少 CD34+细胞群体。NB 肿瘤中 NCL 表达水平升高与患者预后不良相关。总之,这些结果表明,NCL 可能是盐霉素的一个新的功能性结合靶标,有望成为 NB 治疗的预后标志物。