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N-CoR Pathway Targeting Induces Glioblastoma Derived Cancer Stem Cell Differentiation
Deric M. Park, Jie Li, Hiroaki Okamoto, Oluwaseun Akeju, Stephanie H. Kim, Irina Lubensky, Alexander Vortmeyer, James Dambrosia, Robert J. Weil, Edward H. Oldfield, John K. Park and Zhengping Zhuang
volume 6 | issue 4
15 February 2007Pages: 467 - 470
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Nuclear receptor co-repressor (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 co-repressor 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.
Authors
Deric M. Park
National Institutes of Health, Bethesda, MD
Jie Li
National Institutes of Health, Bethesda, MD
Hiroaki Okamoto
National Institutes of Health, Bethesda, MD
Oluwaseun Akeju
National Institutes of Health, Bethesda, MD
Stephanie H. Kim
National Institutes of Health, Bethesda, MD
Irina Lubensky
National Institutes of Health, Bethesda, MD
Alexander Vortmeyer
National Institutes of Health, Bethesda, MD
James Dambrosia
National Institutes of Health, Bethesda, MD
Robert J. Weil
Cleveland Clinic Foundation, Cleveland, Ohio
Edward H. Oldfield
National Institutes of Health, Bethesda, MD
John K. Park
National Institutes of Health, Bethesda, MD
Zhengping Zhuang
National Institutes of Health, Bethesda, MD
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.