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Molecular Cancer Research
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Y-Box Binding Protein-1: A Neglected Target in Pediatric Brain Tumors?

Louisa Taylor, Ian D. Kerr and Beth Coyle
Louisa Taylor
1Children’s Brain Tumour Research Centre, School of Medicine, University of Nottingham Biodiscovery Institute, University of Nottingham, University Park, Nottingham, United Kingdom.
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Ian D. Kerr
2School of Life Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham, United Kingdom.
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Beth Coyle
1Children’s Brain Tumour Research Centre, School of Medicine, University of Nottingham Biodiscovery Institute, University of Nottingham, University Park, Nottingham, United Kingdom.
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  • ORCID record for Beth Coyle
  • For correspondence: beth.coyle@nottingham.ac.uk
DOI: 10.1158/1541-7786.MCR-20-0655 Published March 2021
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Abstract

Brain and central nervous system tumors represent the most common childhood solid tumors. Comprising 21% of all pediatric cancers, they remain the leading cause of cancer-related mortality and morbidity in childhood. Due to advances in neurosurgical technique, radiotherapy and the use of combination therapy, survival rates have generally increased. However, by cause of the lesion itself, its surgical removal and subsequent treatment, survivors are at high risk of long-term neurocognitive sequelae and secondary cancer. Clearly, improvements in diagnosis and treatment are needed. Accordingly, current treatment is evolving away from conventional, uniform therapy and towards risk-stratified regimens and molecularly-targeted therapies, with the aim of diminishing adverse side effects while minimizing the risk of disease recurrence. The multifunctional oncoprotein Y-box binding protein 1 (YB-1) may serve as one such molecular target. Increased YB-1 levels have been reported in a number of pediatric brain tumors, where YB-1 appears to facilitate the advancement of malignant phenotypes. These include proliferation, invasion, and resistance to therapy, as well as the maintenance of brain tumor-initiating cells. Here we evaluate the current literature and show how YB-1 modulates signaling pathways driving each of these phenotypes. We also review the regulation of YB-1 at a transcriptional, translational, posttranslational and subcellular level and argue that there is strong and sufficient evidence to support the development of YB-1 as a biomarker and future therapeutic target in childhood brain tumors.

Footnotes

  • Mol Cancer Res 2021;19:375–87

  • Received July 29, 2020.
  • Revision received October 21, 2020.
  • Accepted November 20, 2020.
  • Published first November 25, 2020.
  • ©2020 American Association for Cancer Research.
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Molecular Cancer Research: 19 (3)
March 2021
Volume 19, Issue 3
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Y-Box Binding Protein-1: A Neglected Target in Pediatric Brain Tumors?
Louisa Taylor, Ian D. Kerr and Beth Coyle
Mol Cancer Res March 1 2021 (19) (3) 375-387; DOI: 10.1158/1541-7786.MCR-20-0655

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Y-Box Binding Protein-1: A Neglected Target in Pediatric Brain Tumors?
Louisa Taylor, Ian D. Kerr and Beth Coyle
Mol Cancer Res March 1 2021 (19) (3) 375-387; DOI: 10.1158/1541-7786.MCR-20-0655
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  • Article
    • Abstract
    • Introduction
    • Medulloblastoma
    • Pediatric Glioma
    • Ependymomas
    • YB-1 in Brain Tumors: A Neglected Therapeutic Target?
    • Structural Organization of YB-1
    • YB-1 Regulation: An Intricate Web of Transcriptional, Translational, and Posttranslational Control
    • YB-1: A Master Regulator of Cancer Cell Biology
    • YB-1 and Pediatric Brain Tumors: Clinical Relevance
    • Conclusion
    • Authors’ Disclosures
    • Acknowledgments
    • Footnotes
    • References
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Molecular Cancer Research
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