Abstract
Increasing evidence suggests that brain tumors arise from the transformation of neural stem/precursor/progenitor cells. Much current research on human brain tumors is focused on the stem-like properties of glioblastoma. Here we show that anaplastic lymphoma kinase (ALK) and its ligand pleiotrophin are required for the self-renewal and tumorigenicity of glioblastoma stem cells (GSCs). Furthermore, we demonstrate that pleiotrophin is transactivated directly by SOX2, a transcription factor essential for the maintenance of both neural stem cells and GSCs. We speculate that the pleiotrophin-ALK axis may be a promising target for the therapy of glioblastoma.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anaplastic Lymphoma Kinase
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Animals
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Brain Neoplasms / genetics
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Brain Neoplasms / metabolism*
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Brain Neoplasms / pathology
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Carcinogenesis / metabolism*
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism
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Cell Proliferation
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Cytokines / genetics*
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Cytokines / metabolism
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Gene Expression Regulation, Neoplastic
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Glioblastoma / genetics
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Glioblastoma / metabolism*
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Glioblastoma / pathology
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HEK293 Cells
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Humans
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Neoplasm Transplantation
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Neoplastic Stem Cells / metabolism*
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Neoplastic Stem Cells / pathology
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Neoplastic Stem Cells / physiology
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Receptor Protein-Tyrosine Kinases / metabolism*
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SOXB1 Transcription Factors / metabolism
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Transcriptional Activation
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Tumor Cells, Cultured
Substances
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Carrier Proteins
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Cytokines
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SOX2 protein, human
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SOXB1 Transcription Factors
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pleiotrophin
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ALK protein, human
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Alk protein, mouse
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Anaplastic Lymphoma Kinase
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Receptor Protein-Tyrosine Kinases