Nanog-induced dedifferentiation of p53-deficient mouse astrocytes into brain cancer stem-like cells

Jai Hee Moon, Suhyun Kwon, Eun Kyoung Jun, Aeree Kim, Kwang Youn Whang, Hyunggee Kim, Sejong Oh, Byung Sun Yoon, Seungkwon You

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Self-renewal, differentiation, and tumorigenicity characterize cancer stem cells (CSCs), which are rare and maintained by specific cell fate regulators. CSCs are isolated from glioblastoma multiforme (GBM) and may be responsible for the lethality of incurable brain tumors. Brain CSCs may arise from the transformation of undifferentiated, nestin-positive neural stem or progenitor cells and GFAP-expressing astrocytes. Here, we report a role of Nanog in the genesis of cancer stem-like cells. Using primary murine p53-knockout astrocytes (p53-/- astrocytes), we provide evidence that enforced Nanog expression can increase the cellular growth rate and transform phenotypes in vitro and in vivo. In addition, Nanog drives p53-/- astrocytes toward a dedifferentiated, CSC-like phenotype with characteristic neural stem cell/progenitor marker expression, neurosphere formation, self-renewal activity, and tumor development. These findings suggest that Nanog promotes dedifferentiation of p53-deficient mouse astrocytes into cancer stem-like cells by changing the cell fate and transforming cell properties.

Original languageEnglish
Pages (from-to)175-181
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume412
Issue number1
DOIs
Publication statusPublished - 2011 Aug 19

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Keywords

  • Brain cancer stem cell-like cells
  • Dedifferentiation
  • Nanog
  • P53 Astrocytes
  • Tumorigenicity

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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