Abstract
Pluripotent cells within embryonal carcinoma (EC) can differentiate in vivo or in vitro on treatment with specific agents. Differentiating EC cells express lower levels of stem cell-related genes, such as Cripto-1. We show that migration of human EC cells (NTERA/2 and NCCIT) can be reduced following treatment with the guidance molecule Netrin-1. Moreover, Netrin-1 treatment increased the levels of beta-III tubulin, glial filament acidic protein, Nestin, and gamma-aminobutyric acid and reduced the expressions of Cripto-1, Nanog, and Oct4 in EC cells. These Netrin-1-induced effects in the EC cells were mediated via binding of Netrin-1 to the Neogenin receptor and activation of SHP-2, resulting in increased levels of inactive phosphorylated c-src((Y527)). These results suggest that Netrin-1 can induce neuroectodermal-like differentiation of human EC cells by affecting c-src signaling via SHP-2 activation and regulation of Nanog, Oct4, and Cripto-1 expressions.
MeSH terms
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Cell Differentiation / drug effects
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Cell Line, Tumor
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Cell Movement / drug effects
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Embryonal Carcinoma Stem Cells / drug effects*
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Embryonal Carcinoma Stem Cells / pathology
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Epidermal Growth Factor / analysis
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GPI-Linked Proteins
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Humans
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Intercellular Signaling Peptides and Proteins
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Membrane Glycoproteins / analysis
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Neoplasm Proteins / analysis
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Nerve Growth Factors / pharmacology*
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Netrin-1
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Octamer Transcription Factor-3 / analysis
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Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism
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Proto-Oncogene Proteins pp60(c-src) / metabolism
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Tumor Suppressor Proteins / pharmacology*
Substances
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GPI-Linked Proteins
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Intercellular Signaling Peptides and Proteins
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Membrane Glycoproteins
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NTN1 protein, human
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Neoplasm Proteins
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Nerve Growth Factors
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Octamer Transcription Factor-3
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POU5F1 protein, human
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TDGF1 protein, human
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Tumor Suppressor Proteins
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Netrin-1
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Epidermal Growth Factor
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Proto-Oncogene Proteins pp60(c-src)
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PTPN11 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 11