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Growth Factors. 2012 Feb;30(1):13-21. doi: 10.3109/08977194.2011.641962. Epub 2011 Dec 12.

An evolving web of signaling networks regulated by Cripto-1.

Author information

1
Tumor Growth Factor Section, Laboratory of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Abstract

Over the past few decades, our understanding of the embryonic gene Cripto-1 has considerably advanced through biochemical, cell biology, and animal studies. Cripto-1 performs key functions during embryonic development, while it dramatically disappears in adult tissues, except possibly in adult tissue stem cells. Cripto-1 is re-expressed in human tumors promoting cell proliferation, migration, invasion, epithelial to mesenchymal transition, and tumor angiogenesis. This diversity of biological effects is dependent upon interaction of Cripto-1 with an extensive array of signaling molecules. In fact, Cripto-1 modulates signaling of transforming growth factor-β family members, including Nodal, GDF-1/-3, Activin, and TGF-β1, activates c-src/MAPK/Protein Kinase B (AKT) pathway in a Glypican-1 and GRP78-dependent manner, and cross-talks with erbB4, Wnt/β-catenin, Notch, Caveolin-1, and Apelin/putative receptor protein related to Angiotensin-type I receptor (APJ) pathways. This article provides an updated survey of the various signaling pathways modulated by Cripto-1 with a focus on mechanistic insights in our understanding of the biological function of Cripto-1 in eukaryotic cells.

PMID:
22149969
DOI:
10.3109/08977194.2011.641962
[Indexed for MEDLINE]

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