Activation of a Nodal-independent signaling pathway by Cripto-1 mutants with impaired activation of a Nodal-dependent signaling pathway

Bianco, Caterina; Mysliwiec, Margaret; Watanabe, Kazuhide; Mancino, Mario; Nagaoka, Tadahiro; Gonzales, Monica; Salomon, David S.

doi:10.1016/j.febslet.2008.10.052

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Volume 582, Issue 29 , Pages 3997-4002, 10 December 2008

Activation of a Nodal-independent signaling pathway by Cripto-1 mutants with impaired activation of a Nodal-dependent signaling pathway

Edited by Lukas Huber

Mammary Biology and Tumorigenesis Laboratory, NCI/NIH, 37 Convent Drive, Building 37 room 1112, Bethesda, MD 20892, USA

Received 11 September 2008; received in revised form 23 October 2008; accepted 31 October 2008. published online 13 November 2008.

Abstract

Cripto-1, a co-receptor for Nodal, can activate Nodal-dependent and Nodal-independent signaling pathways. In this study we have investigated whether Cripto-1 mutants, that fail to activate a Nodal-dependent signaling pathway, are capable to activate a Nodal-independent signaling pathway in mammary epithelial cells. Cripto-1 mutants expressed in EpH4 mouse mammary epithelial cells are fully functional in regard to activation of a Nodal-independent signaling pathway, leading to phosphorylation of mitogen-activated protein kinase (MAPK) and Akt and to enhanced proliferation and motility of these cells, suggesting that Cripto-1 mutants with impaired Nodal signaling are still active in a Nodal-independent signaling pathway.