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

Research output: Contribution to journalArticlepeer-review


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
Pages (from-to)1717-1721
Number of pages5
JournalCancer Research
Issue number5
Publication statusPublished - Mar 1 2009

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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