N-CoR pathway targeting induces glioblastoma derived cancer stem cell differentiation. Academic Article uri icon

Overview

abstract

  • Nuclear receptor corepressor (N-CoR) is a critical regulator of neural stem cell differentiation. Nuclear localization of N-CoR is a feature of undifferentiated neural stem cells and cytoplasmic translocation of N-CoR leads to astrocytic differentiation. Comparative proteomic analysis of microdissected glioblastoma multiforme (GBM) specimens and matched normal glial tissue reveals increased expression of N-CoR in GBM. In GBM primary cell cultures, tumor cells with nuclear localization of N-CoR demonstrate an undifferentiated phenotype, but are subject to astroglial differentiation upon exposure to agents promoting phosphorylation of N-CoR and its subsequent translocation to the cytoplasm. Treatment of glioma cell lines with a combination of retinoic acid and low-dose okadaic acid decreases the corepressor effect of N-CoR and has a striking synergistic effect on growth inhibition. The identification of N-CoR in GBM provides insights into the tumorigenesis process and supports the development of differentiation-based therapeutic strategies.

publication date

  • February 12, 2007

Research

keywords

  • Brain Neoplasms
  • Glioblastoma
  • Neoplastic Stem Cells
  • Nuclear Proteins
  • Repressor Proteins

Identity

Scopus Document Identifier

  • 33847776362

Digital Object Identifier (DOI)

  • 10.4161/cc.6.4.3856

PubMed ID

  • 17312396

Additional Document Info

volume

  • 6

issue

  • 4