Role of Cripto-1 in stem cell maintenance and malignant progression

Am J Pathol. 2010 Aug;177(2):532-40. doi: 10.2353/ajpath.2010.100102. Epub 2010 Jul 8.


Cripto-1 is critical for early embryonic development and, together with its ligand Nodal, has been found to be associated with the undifferentiated status of mouse and human embryonic stem cells. Like other embryonic genes, Cripto-1 performs important roles in the formation and progression of several types of human tumors, stimulating cell proliferation, migration, epithelial to mesenchymal transition, and tumor angiogenesis. Several studies have demonstrated that cell fate regulation during embryonic development and cell transformation during oncogenesis share common signaling pathways, suggesting that uncontrolled activation of embryonic signaling pathways might drive cell transformation and tumor progression in adult tissues. Here we review our current understanding of how Cripto-1 controls stem cell biology and how it integrates with other major embryonic signaling pathways. Because many cancers are thought to derive from a subpopulation of cancer stem-like cells, which may re-express embryonic genes, Cripto-1 signaling may drive tumor growth through the generation or expansion of tumor initiating cells bearing stem-like characteristics. Therefore, the Cripto-1/Nodal signaling may represent an attractive target for treatment in cancer, leading to the elimination of undifferentiated stem-like tumor initiating cells.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Disease Progression*
  • Embryonic Development
  • Epidermal Growth Factor / genetics
  • Epidermal Growth Factor / metabolism*
  • Epithelial-Mesenchymal Transition
  • GPI-Linked Proteins
  • Humans
  • Hypoxia
  • Intercellular Signaling Peptides and Proteins
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasms / pathology*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Nodal Protein / genetics
  • Nodal Protein / metabolism
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism
  • Signal Transduction / physiology
  • Stem Cells / physiology*
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism


  • GPI-Linked Proteins
  • Intercellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • Nodal Protein
  • Receptors, Notch
  • TDGF1 protein, human
  • Wnt Proteins
  • Epidermal Growth Factor