Document Detail

Cripto-1 enhances the canonical Wnt/β-catenin signaling pathway by binding to LRP5 and LRP6 co-receptors.
MedLine Citation:
PMID:  23022962     Owner:  NLM     Status:  MEDLINE    
Cripto-1 is implicated in multiple cellular events, including cell proliferation, motility and angiogenesis, through the activation of an intricate network of signaling pathways. A crosstalk between Cripto-1 and the canonical Wnt/β-catenin signaling pathway has been previously described. In fact, Cripto-1 is a downstream target gene of the canonical Wnt/β-catenin signaling pathway in the embryo and in colon cancer cells and T-cell factor (Tcf)/lymphoid enhancer factor binding sites have been identified in the promoter and the first intronic region of the mouse and human Cripto-1 genes. We now demonstrate that Cripto-1 modulates signaling through the canonical Wnt/β-catenin/Tcf pathway by binding to the Wnt co-receptors low-density lipoprotein receptor-related protein (LRP) 5 and LRP6, which facilitates Wnt3a binding to LRP5 and LRP6. Cripto-1 functionally enhances Wnt3a signaling through cytoplasmic stabilization of β-catenin and elevated β-catenin/Tcf transcriptional activation. Conversely, Wnt3a further increases Cripto-1 stimulation of migration, invasion and colony formation in soft agar of HC11 mouse mammary epithelial cells, indicating that Cripto-1 and the canonical Wnt/β-catenin signaling co-operate in regulating motility and in vitro transformation of mammary epithelial cells.
Tadahiro Nagaoka; Hideaki Karasawa; Thomas Turbyville; Maria-Cristina Rangel; Nadia P Castro; Monica Gonzales; Alyson Baker; Masaharu Seno; Stephen Lockett; Yoshimi E Greer; Jeffrey S Rubin; David S Salomon; Caterina Bianco
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural     Date:  2012-09-27
Journal Detail:
Title:  Cellular signalling     Volume:  25     ISSN:  1873-3913     ISO Abbreviation:  Cell. Signal.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-11-26     Completed Date:  2013-04-30     Revised Date:  2014-01-10    
Medline Journal Info:
Nlm Unique ID:  8904683     Medline TA:  Cell Signal     Country:  England    
Other Details:
Languages:  eng     Pagination:  178-89     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Inc.
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MeSH Terms
Cell Line
Cell Movement
GPI-Linked Proteins / chemistry,  metabolism*
HEK293 Cells
Intercellular Signaling Peptides and Proteins / chemistry,  metabolism*
Low Density Lipoprotein Receptor-Related Protein-5 / genetics,  metabolism*
Low Density Lipoprotein Receptor-Related Protein-6 / genetics,  metabolism*
Neoplasm Proteins / chemistry,  metabolism*
Protein Binding
Protein Structure, Tertiary
Smad2 Protein / metabolism
Smad3 Protein / metabolism
Transcriptional Activation
Wnt Signaling Pathway*
Wnt3A Protein / metabolism
beta Catenin / metabolism
Grant Support
HHSN261200800001E//PHS HHS; Z99 CA999999/CA/NCI NIH HHS
Reg. No./Substance:
0/Dkk1 protein, mouse; 0/GPI-Linked Proteins; 0/Intercellular Signaling Peptides and Proteins; 0/Low Density Lipoprotein Receptor-Related Protein-5; 0/Low Density Lipoprotein Receptor-Related Protein-6; 0/Neoplasm Proteins; 0/Smad2 Protein; 0/Smad3 Protein; 0/TDGF1 protein, human; 0/Wnt3A Protein; 0/beta Catenin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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