Elsevier

Molecules and Cells

Volume 30, Issue 5, November 2010, Pages 403-408
Molecules and Cells

The Neural Stem Cell Fate Determinant TLX Promotes Tumorigenesis and Genesis of Cells Resembling Glioma Stem Cells

https://doi.org/10.1007/s10059-010-0122-zGet rights and content
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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 tumori- genic 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.

Keywords:

cancer stem cells
cyclin D1
glioma
TLX
Tumorigenesis

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