title: An evolving web of signaling networks regulated by Cripto-1.
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.
authors.affiliation: Tumor Growth Factor Section, Laboratory of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Nagaoka
authors.forename: Hideaki
authors.initials: H
authors.lastname: Karasawa
authors.forename: Nadia Pereira
authors.initials: NP
authors.lastname: Castro
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Rangel
authors.forename: David S
authors.initials: DS
authors.lastname: Salomon
authors.forename: Caterina
authors.initials: C
authors.lastname: Bianco
mesh_terms: D000818:Animals; D006224:Cricetinae; D047108:Embryonic Development / Q000187:drug effects*; D000091342:Endoplasmic Reticulum Chaperone BiP; D058851:GPI-Linked Proteins / Q000378:metabolism / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism / Q000494:pharmacology*; D009369:Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D058851:GPI-Linked Proteins; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C070636:TDGF1 protein, human