转录分析显示高危险的人类神经母细胞瘤和小鼠神经母细胞瘤的球形细胞中有共同的代谢调节  

Transcriptional Profiling Reveals a Common Metabolic Program in High-Risk Human Neuroblastoma and Mouse Neuroblastoma Sphere-Forming Cells

作　　者：Mengling Liu Yingfeng Xia Jane Ding Bingwei Ye Erhu Zhao Jeong-Hyeon Choi Ahmet Alptekin Chunhong Yan Zheng Dong Shuang Huang Liqun Yang Hongjuan Cui 查运红 Han-Fei Ding 

机构地区：[1]不详 [2]宜昌市第一人民医院/三峡大学人民医院神经内科 [3]三峡大学

出　　处：《科学新闻》2017年第4期161-161,共1页Science News

基　　金：美国国立卫生研究院;美国国防部给予Han-Fei Ding;国家自然科学基金给予查运红的资助

摘　　要：高危险性的神经母细胞瘤（neuroblastoma）仍然是一种最致命的幼童癌症之一，而识别驱动或维持高危险性的神经母细胞瘤的代谢途径则可能开辟新的治疗方针。High-risk neuroblastoma remains one of the deadliest childhood cancers. Identification of metabolic pathways that drive or maintain high-risk neuroblastoma may open new avenues of therapeutic interventions. Here, we report the isolation and propagation of neuroblastoma sphere-forming cells with self-renewal and differentiation potential from tumors of the TH-MYCN mouse, an animal model of high-risk neuroblastoma with MYCN amplification. Transcriptional profiling reveals that mouse neuroblastoma sphere-forming cells acquire a metabolic program characterized by transcriptional activation of the cholesterol and serine-glycine synthesis pathways, primarily as a result of increased expression of sterol regulatory element binding factors and Atf4, respectively. This metabolic reprogramming is recapitulated in high-risk human neuroblastomas and is prognostic for poor clinical outcome. Genetic and pharmacological inhibition of the metabolic program markedly decreases the growth and tumorigenicity of both mouse neuroblastoma sphere-forming cells and human neuroblastoma cell lines. These findings suggest a therapeutic strategy for targeting the metabolic program of high-risk neuroblastoma.

关 键 词：危险性 细胞 神经 代谢 小鼠 人类 显示 转录 

分 类 号：Q26[生物学—细胞生物学]