TY - JOUR
T1 - Neuronal guidance protein netrin-1 induces differentiation in human embryonal carcinoma cells
AU - Mancino, Mario
AU - Esposito, Claudia
AU - Watanabe, Kazuhide
AU - Nagaoka, Tadahiro
AU - Gonzales, Monica
AU - Bianco, Caterina
AU - Normanno, Nicola
AU - Salomon, David S.
AU - Strizzi, Luigi
PY - 2009/3/1
Y1 - 2009/3/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=62449298017&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-08-2985
DO - 10.1158/0008-5472.CAN-08-2985
M3 - Article
C2 - 19223540
AN - SCOPUS:62449298017
SN - 0008-5472
VL - 69
SP - 1717
EP - 1721
JO - Cancer Research
JF - Cancer Research
IS - 5
ER -
