Neuronal guidance protein netrin-1 induces differentiation in human embryonal carcinoma cells

Mario Mancino*, Claudia Esposito, Kazuhide Watanabe, Tadahiro Nagaoka, Monica Gonzales, Caterina Bianco, Nicola Normanno, David S. Salomon, Luigi Strizzi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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 (NTEBA/2 and NCCIT) can be reduced following treatment with the guidance molecule Netrin-1. Moreover, Netrin-1 treatment increased the levels of ß-III tubulin, glial filament acidic protein, Nestin, and 7-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(YS27). 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.

Original languageEnglish (US)
Pages (from-to)1717-1721
Number of pages5
JournalCancer Research
Issue number5
StatePublished - Mar 1 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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