The neural stem cell fate determinant TLX promotes tumorigenesis and genesis of cells resembling glioma stem cells

Hyo Jung Park, Jun Kyum Kim, Hye Min Jeon, Se Yeong Oh, Sung Hak Kim, Myung Jin Park, Akio Soeda, Do Hyun Nam, Hyunggee Kim

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

A growing body of evidence indicates that deregulation of stem cell fate determinants is a hallmark of many types of malignancies. The neural stem cell fate determinant TLX plays a pivotal role in neurogenesis in the adult brain by maintaining neural stem cells. Here, we report a tumorigenic role of TLX in brain tumor initiation and progression. Increased TLX expression was observed in a number of glioma cells and glioma stem cells, and correlated with poor survival of patients with gliomas. Ectopic expression of TLX in the U87MG glioma cell line and Ink4a/Arf-deficient mouse astrocytes (Ink4a/Arf-/- astrocytes) induced cell proliferation with a concomitant increase in cyclin D expression, and accelerated foci formation in soft agar and tumor formation in in vivo transplantation assays. Furthermore, overexpression of TLX in Ink4a/Arf-/- astrocytes inhibited cell migration and invasion and promoted neurosphere formation and Nestin expression, which are hallmark characteristics of glioma stem cells, under stem cell culture conditions. Our results indicate that TLX is involved in glioma stem cell genesis and represents a potential therapeutic target for this type of malignancy.

Original languageEnglish
Pages (from-to)403-408
Number of pages6
JournalMolecules and Cells
Volume30
Issue number5
DOIs
Publication statusPublished - 2010 Nov 1

Fingerprint

Neural Stem Cells
Glioma
Carcinogenesis
Stem Cells
Astrocytes
Cyclin D
Nestin
Neoplasms
Neurogenesis
Brain Neoplasms
Agar
Cell Movement
Cell Culture Techniques
Cell Count
Transplantation
Cell Proliferation
Cell Line
Survival
Brain

Keywords

  • cancer stem cells
  • cyclin D1
  • glioma
  • TLX
  • Tumorigenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

The neural stem cell fate determinant TLX promotes tumorigenesis and genesis of cells resembling glioma stem cells. / Park, Hyo Jung; Kim, Jun Kyum; Jeon, Hye Min; Oh, Se Yeong; Kim, Sung Hak; Park, Myung Jin; Soeda, Akio; Nam, Do Hyun; Kim, Hyunggee.

In: Molecules and Cells, Vol. 30, No. 5, 01.11.2010, p. 403-408.

Research output: Contribution to journalArticle

Park, Hyo Jung ; Kim, Jun Kyum ; Jeon, Hye Min ; Oh, Se Yeong ; Kim, Sung Hak ; Park, Myung Jin ; Soeda, Akio ; Nam, Do Hyun ; Kim, Hyunggee. / The neural stem cell fate determinant TLX promotes tumorigenesis and genesis of cells resembling glioma stem cells. In: Molecules and Cells. 2010 ; Vol. 30, No. 5. pp. 403-408.
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