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

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, Yunhong Zha, Han Fei Ding

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)609-623
Number of pages15
JournalCell Reports
Volume17
Issue number2
DOIs
StatePublished - Oct 4 2016

Fingerprint

Neuroblastoma
Sterols
Glycine
Serine
Amplification
Tumors
Animals
Chemical activation
Cholesterol
Cells
Metabolic Networks and Pathways
Transcriptional Activation
Neoplasms
Animal Models
Pharmacology
Cell Line
Therapeutics
Growth

Keywords

  • MYCN
  • TH-MYCN mouse
  • cancer metabolism
  • cholesterol biosynthesis
  • high-risk neuroblastoma
  • mevalonate pathway
  • neuroblastoma stem cells
  • serine-glycine biosynthesis
  • statin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Transcriptional Profiling Reveals a Common Metabolic Program in High-Risk Human Neuroblastoma and Mouse Neuroblastoma Sphere-Forming Cells. / Liu, Mengling; Xia, Yingfeng; Ding, Jane; Ye, Bingwei; Zhao, Erhu; Choi, Jeong Hyeon; Alptekin, Ahmet; Yan, Chunhong; Dong, Zheng; Huang, Shuang; Yang, Liqun; Cui, Hongjuan; Zha, Yunhong; Ding, Han Fei.

In: Cell Reports, Vol. 17, No. 2, 04.10.2016, p. 609-623.

Research output: Contribution to journalArticle

Liu, Mengling ; Xia, Yingfeng ; Ding, Jane ; Ye, Bingwei ; Zhao, Erhu ; Choi, Jeong Hyeon ; Alptekin, Ahmet ; Yan, Chunhong ; Dong, Zheng ; Huang, Shuang ; Yang, Liqun ; Cui, Hongjuan ; Zha, Yunhong ; Ding, Han Fei. / Transcriptional Profiling Reveals a Common Metabolic Program in High-Risk Human Neuroblastoma and Mouse Neuroblastoma Sphere-Forming Cells. In: Cell Reports. 2016 ; Vol. 17, No. 2. pp. 609-623.
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