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Native Chromatin Immunoprecipitation Using Murine Brain Tumor Neurospheres
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Published on: January 29, 2018

DNER, an epigenetically modulated gene, regulates glioblastoma-derived neurosphere cell differentiation and tumor

Peng Sun1, Shuli Xia, Bachchu Lal

  • 1Department of Neurology, The Johns Hopkins University School of Medicine and The Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, Maryland 21205, USA.

Stem Cells (Dayton, Ohio)
|June 23, 2009
PubMed

Insights

Histone deacetylase inhibitors reduce glioblastoma stem-like cell growth and promote differentiation. A key mediator, Delta/Notch-like epidermal growth factor-related receptor (DNER), exhibits tumor-suppressive effects via noncanonical Notch signaling.

Area of Science:

  • Neuro-oncology
  • Cancer Stem Cell Biology
  • Epigenetics

Background:

  • Glioblastoma (GBM) stem-like cells drive tumor growth and therapeutic resistance.
  • Understanding the regulation of these stem-like cells is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role of histone-modifying agents in regulating GBM stem-like cell phenotype and tumor-promoting capacity.
  • To elucidate the mechanisms underlying GBM stem-like cell regulation.

Main Methods:

  • Utilized established and primary glioblastoma-derived neurosphere lines.
  • Administered histone deacetylase (HDAC) inhibitors.
  • Analyzed the expression and function of Delta/Notch-like epidermal growth factor-related receptor (DNER).
  • Evaluated effects on cell growth, differentiation, apoptosis, and tumor xenograft formation in vivo and in vitro.

Main Results:

  • HDAC inhibitors suppressed growth, induced differentiation, and promoted apoptosis in GBM neurosphere cells.
  • HDAC inhibition upregulated DNER expression.
  • DNER inhibited GBM neurosphere growth, induced differentiation, and reduced tumor xenograft formation.
  • DNER's tumor-suppressive effects contrast with canonical Notch signaling's known tumor-promoting role.

Conclusions:

  • Noncanonical Notch signaling, mediated by DNER, plays a role in regulating neoplastic stem-like cells.
  • HDAC inhibitors and DNER represent potential therapeutic strategies for targeting glioblastoma stem-like cells.
  • Findings suggest novel treatment avenues for glioblastoma and other solid malignancies.

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