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

Authors
Park, Hyo-JungKim, Jun-KyumJeon, Hye-MinOh, Se-YeongKim, Sung-HakPark, Myung-JinSoeda, AkioNam, Do-HyunKim, Hyunggee
Issue Date
11월-2010
Publisher
KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
Keywords
cancer stem cells; cyclin D1; glioma; TLX; Tumorigenesis
Citation
MOLECULES AND CELLS, v.30, no.5, pp.403 - 408
Indexed
SCIE
SCOPUS
KCI
Journal Title
MOLECULES AND CELLS
Volume
30
Number
5
Start Page
403
End Page
408
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/115465
DOI
10.1007/s10059-010-0122-z
ISSN
1016-8478
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.
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