An evolving web of signaling networks regulated by Cripto-1

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


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Cricetinae
  • Embryonic Development / drug effects*
  • GPI-Linked Proteins / metabolism
  • GPI-Linked Proteins / pharmacology*
  • Gene Expression Regulation
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Mice
  • Neoplasm Proteins / metabolism
  • Neoplasm Proteins / pharmacology*
  • Neoplasms / metabolism
  • Neoplasms / physiopathology*
  • Signal Transduction / drug effects*


  • GPI-Linked Proteins
  • Intercellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • TDGF1 protein, human