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Human embryonic stem cell-derived neural crest model unveils CD55 as a cancer stem cell regulator for therapeutic targeting in MYCN-amplified neuroblastoma.

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资源类型：
Pubmed体系：
作者：
Zhihui Weng[1,3] ; Jiacheng Lin[1,3] ; Jiaozi He[5] ; Lin Gao[1,3] ; Sien Lin[2,3] ; Lai Ling Tsang[1,3] ; Hang Zhang[7] ; Xiaoyan He[7] ; Guang Wang[6] ; Xuesong Yang[6] ; Hu Zhou[8] ; Hui Zhao[1,3] ; Gang Li[2,3] ; Lin Zou[7] ; Xiaohua Jiang[1,3,4] ;
机构： [1]Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, [2]Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China. [3]The Chinese University of Hong Kong, Shenzhen Research Institute, ShenZhen, PR China.Faculty of Medicine, The Chinese University of Hong Kong. [4]Sichuan University-The Chinese University of Hong Kong Joint Laboratory for Reproductive Medicine, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China. [5]Department of Clinical Oncology, Faculty of Medicine, The University of Hong Kong, Hong Kong. [6]Department of Histology and Embryology, International Joint Laboratory for Embryonic Development & Prenatal Medicine, Medical College, Jinan University, Guangzhou 510632, PR China. [7]Center for Clinical Molecular Medicine, Children’s Hospital, Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, 400014, PR China. [8]School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian, 361102, China.
出处：
DOI： 10.1093/neuonc/noab241
ISSN：

关键词： neuroblastoma disease model human embryonic stem cells MYCN CD55

摘要：
Neuroblastoma (NB) is a common childhood malignant tumor of neural crest (NC) origin with remarkable heterogeneity in outcomes. Amplification of the oncogene MYCN is strongly associated with highly malignant behaviour and poor prognosis.This study aims to use a human embryonic stem cell (hESC)-derived NC model to identify novel downstream effectors of MYCN that can be potentially used as prognostic and/or therapeutic target.We show that MYCN-driven NB derived from human neural crest cells (hNCCs) recapitulate the pathological and molecular features of MYCN-amplified neuroblastoma (MNA-NB). By using this platform, we identify a group of 14 surface protein encoding-genes that are associated with MYCN expression level in MNA-NB. Among these genes, high CD55 expression is correlated with poor survival in MNA-NB but not in non-MNA-NB. Furthermore, CD55 promotes tumorigenesis, tumor growth and cancer stemness in MNA-NB cell lines (MNA-NBL) through regulating the JNK pathway. Mechanistically, MYCN binds to both canonical and non-canonical E-boxes on the promoter of CD55 to regulate its transcriptional expression. Finally, neutralizing antibody targeting CD55 significantly attenuates cancer stemness, suppresses tumor growth and improves survival exclusively in MNA-NBL-inoculated mice.MYCN shapes CD55 into a novel cancer stem cell regulator which represents a prognostic marker and therapeutic target of MNA-NB. The hESC-derived NC model serves as a valuable platform for investigating NB initiation and progression and developing potential therapeutic targets.© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

基金：
This work is supported by UGC/GRF (14111519, 14165217, 466710) and Hong Kong Innovation and Technology Commission (ITS/448/18, MHP/024/19). The work is also supported by National Natural Science Foundation of China (NSFC No. 31970815, 31771517) and Guang Dong Province Science and Technology Grants (2018B030311065).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类 | 1 区 医学
小类 | 1 区 肿瘤学 1 区 临床神经病学
最新[2023]版：
大类 | 1 区 医学
小类 | 1 区 临床神经病学 1 区 肿瘤学
第一作者：
第一作者机构： [1]Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, [3]The Chinese University of Hong Kong, Shenzhen Research Institute, ShenZhen, PR China.Faculty of Medicine, The Chinese University of Hong Kong.
共同第一作者：
推荐引用方式(GB/T 7714)：
Zhihui Weng,Jiacheng Lin,Jiaozi He,et al.Human embryonic stem cell-derived neural crest model unveils CD55 as a cancer stem cell regulator for therapeutic targeting in MYCN-amplified neuroblastoma.[J].Neuro-oncology.2021,doi:10.1093/neuonc/noab241.
APA：
Zhihui Weng,Jiacheng Lin,Jiaozi He,Lin Gao,Sien Lin...&Xiaohua Jiang.(2021).Human embryonic stem cell-derived neural crest model unveils CD55 as a cancer stem cell regulator for therapeutic targeting in MYCN-amplified neuroblastoma..Neuro-oncology,,
MLA：
Zhihui Weng,et al."Human embryonic stem cell-derived neural crest model unveils CD55 as a cancer stem cell regulator for therapeutic targeting in MYCN-amplified neuroblastoma.".Neuro-oncology .(2021)

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