The neural stem cell fate determinant TLX promotes tumorigenesis and genesis of cells resembling glioma stem cells
Autor: | 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 |
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Rok vydání: | 2010 |
Předmět: |
Adult
Neurogenesis Mice Nude Receptors Cytoplasmic and Nuclear Nerve Tissue Proteins Cell Growth Processes Astrocytoma Biology Central Nervous System Neoplasms Nestin Mice Intermediate Filament Proteins Neural Stem Cells Cell Movement Cancer stem cell Cell Line Tumor Cyclin D Neurosphere Glioma medicine Animals Humans Neoplasm Invasiveness Neoplasm Metastasis neoplasms Molecular Biology Brain Neoplasms Cell Biology General Medicine Orphan Nuclear Receptors Prognosis medicine.disease Neural stem cell Up-Regulation Cell biology Endothelial stem cell Cell Transformation Neoplastic Astrocytes Neoplastic Stem Cells Cancer research Stem cell Adult stem cell |
Zdroj: | Molecules and Cells. 30:403-408 |
ISSN: | 0219-1032 1016-8478 |
DOI: | 10.1007/s10059-010-0122-z |
Popis: | 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. |
Databáze: | OpenAIRE |
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