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, Hanfei 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, Hanfei.

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, Hanfei. / 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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