Journal
CELL CYCLE
Volume 6, Issue 4, Pages 467-470Publisher
LANDES BIOSCIENCE
DOI: 10.4161/cc.6.4.3856
Keywords
N-CoR; glioma; cancer stem cell; differentiation; retinoic acid
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Funding
- Intramural NIH HHS Funding Source: Medline
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Nuclear receptor corepressor (N-CoR) is a critical regulator of neural stem cell differ entiation. 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.
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