Nodal and Cripto-1: embryonic pattern formation genes involved in mammary gland development and tumorigenesis.
Members of the TGFbeta superfamily and EGF-CFC family, such as Nodal and Cripto, are important mediators of anterior-posterior and left-right axis specification during embryogenesis. In this paper, we review the role of Nodal and Cripto as critical morphogen-like molecules, with an emphasis on Nodal and EGF-CFC signaling during embryonic pattern formation. New evidence from gene expression and transgenic mouse studies have shown that both Nodal and Cripto-1 are expressed within the mammary duct and that modulation of these genes can disrupt normal branching morphogenesis resulting in epithelial disorganization and defective ductal architecture. We describe these new findings and propose that Cripto and Nodal are candidate mammary morphogens. Finally, the data linking overexpression of Cripto and perturbations of Cripto signaling to cell transformation and tumor formation are discussed. The fact that Cripto can modulate multiple pathways suggests it may act to deregulate growth inhibitors/homeostasis factors early in the cell transformation process and then activate prosurvival pathways dependent on MAPK and PI3K/Akt later in fully transformed phenotypes.
Kenney
Nicholas J
NJ
Department of Biological Sciences, Hampton University, Hampton, Virginia 23668, USA. nicholas.kenney@hamptonu.edu
Adkins
Heather B
HB
Sanicola
Michele
M
D000818:Animals; D019521:Body Patterning; D001940:Breast / Q000196:embryology*; D001943:Breast Neoplasms / Q000209:etiology*; D004815:Epidermal Growth Factor / Q000502:physiology*; D058851:GPI-Linked Proteins; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008321:Mammary Glands, Animal / Q000196:embryology*; D015674:Mammary Neoplasms, Animal / Q000209:etiology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D009363:Neoplasm Proteins / Q000502:physiology*; D055457:Nodal Protein; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology*
D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C526007:NODAL protein, human; D009363:Neoplasm Proteins; D055457:Nodal Protein; C526008:Nodal protein, mouse; C070636:TDGF1 protein, human; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor