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, Zhengping Zhuang

Research output: Contribution to journalArticle

46 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)467-470
Number of pages4
JournalCell Cycle
Volume6
Issue number4
DOIs
StatePublished - Feb 15 2007
Externally publishedYes

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Co-Repressor Proteins
Neoplastic Stem Cells
Glioblastoma
Cell Differentiation
Neural Stem Cells
Okadaic Acid
Primary Cell Culture
Cytoplasmic and Nuclear Receptors
Tretinoin
Glioma
Neuroglia
Proteomics
Carcinogenesis
Cytoplasm
Phosphorylation
Phenotype
Cell Line

Keywords

  • Cancer stem cell
  • Differentiation
  • Glioma
  • N-CoR
  • Retinoic acid

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Park, D. M., Li, J., Okamoto, H., Akeju, O., Kim, S. H., Lubensky, I., ... Zhuang, Z. (2007). N-CoR pathway targeting induces glioblastoma derived cancer stem cell differentiation. Cell Cycle, 6(4), 467-470. https://doi.org/10.4161/cc.6.4.3856

N-CoR pathway targeting induces glioblastoma derived cancer stem cell differentiation. / Park, Deric M.; Li, Jie; Okamoto, Hiroaki; Akeju, Oluwaseun; Kim, Stephanie H.; Lubensky, Irina; Vortmeyer, Alexander; Dambrosia, James; Weil, Robert J.; Oldfield, Edward H.; Park, John K.; Zhuang, Zhengping.

In: Cell Cycle, Vol. 6, No. 4, 15.02.2007, p. 467-470.

Research output: Contribution to journalArticle

Park, DM, Li, J, Okamoto, H, Akeju, O, Kim, SH, Lubensky, I, Vortmeyer, A, Dambrosia, J, Weil, RJ, Oldfield, EH, Park, JK & Zhuang, Z 2007, 'N-CoR pathway targeting induces glioblastoma derived cancer stem cell differentiation', Cell Cycle, vol. 6, no. 4, pp. 467-470. https://doi.org/10.4161/cc.6.4.3856
Park DM, Li J, Okamoto H, Akeju O, Kim SH, Lubensky I et al. N-CoR pathway targeting induces glioblastoma derived cancer stem cell differentiation. Cell Cycle. 2007 Feb 15;6(4):467-470. https://doi.org/10.4161/cc.6.4.3856
Park, Deric M. ; Li, Jie ; Okamoto, Hiroaki ; Akeju, Oluwaseun ; Kim, Stephanie H. ; Lubensky, Irina ; Vortmeyer, Alexander ; Dambrosia, James ; Weil, Robert J. ; Oldfield, Edward H. ; Park, John K. ; Zhuang, Zhengping. / N-CoR pathway targeting induces glioblastoma derived cancer stem cell differentiation. In: Cell Cycle. 2007 ; Vol. 6, No. 4. pp. 467-470.
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