title: Neuronal guidance protein Netrin-1 induces differentiation in human embryonal carcinoma cells.
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.
authors.affiliation: Mammary Biology and Tumorigenesis Laboratory, National Cancer Institute, Bethesda, Maryland 20892, USA. mario.mancino@cro-m.eu
authors.forename: Mario
authors.initials: M
authors.lastname: Mancino
authors.forename: Claudia
authors.initials: C
authors.lastname: Esposito
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Watanabe
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Nagaoka
authors.forename: Monica
authors.initials: M
authors.lastname: Gonzales
authors.forename: Caterina
authors.initials: C
authors.lastname: Bianco
authors.forename: Nicola
authors.initials: N
authors.lastname: Normanno
authors.forename: David S
authors.initials: DS
authors.lastname: Salomon
authors.forename: Luigi
authors.initials: L
authors.lastname: Strizzi
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D054278:Embryonal Carcinoma Stem Cells / Q000187:drug effects* / Q000473:pathology; D004815:Epidermal Growth Factor / Q000032:analysis; D058851:GPI-Linked Proteins; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000032:analysis; D009363:Neoplasm Proteins / Q000032:analysis; D009414:Nerve Growth Factors / Q000494:pharmacology*; D000075388:Netrin-1; D050814:Octamer Transcription Factor-3 / Q000032:analysis; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000494:pharmacology*
chemical_list: D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C000617351:NTN1 protein, human; D009363:Neoplasm Proteins; D009414:Nerve Growth Factors; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C070636:TDGF1 protein, human; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D004815:Epidermal Growth Factor; D016392:Proto-Oncogene Proteins pp60(c-src); C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11