Cripto-1 enhances the canonical Wnt/β-catenin signaling pathway by binding to LRP5 and LRP6 co-receptors

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

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)178-189
Number of pages12
JournalCellular Signalling
Volume25
Issue number1
DOIs
Publication statusPublished - 01-01-2013
Externally publishedYes

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Catenins
Wnt Signaling Pathway
TCF Transcription Factors
Low Density Lipoprotein Receptor-Related Protein-5
Breast
Wnt Receptors
Epithelial Cells
Colonic Neoplasms
Transcriptional Activation
Genes
Agar
Cell Movement
Embryonic Structures
Binding Sites
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Nagaoka, Tadahiro ; Karasawa, Hideaki ; Turbyville, Thomas ; Rangel, Maria Cristina ; Castro, Nadia P. ; Gonzales, Monica ; Baker, Alyson ; Seno, Masaharu ; Lockett, Stephen ; Greer, Yoshimi E. ; Rubin, Jeffrey S. ; Salomon, David S. ; Bianco, Caterina. / Cripto-1 enhances the canonical Wnt/β-catenin signaling pathway by binding to LRP5 and LRP6 co-receptors. In: Cellular Signalling. 2013 ; Vol. 25, No. 1. pp. 178-189.
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abstract = "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.",
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Nagaoka, T, Karasawa, H, Turbyville, T, Rangel, MC, Castro, NP, Gonzales, M, Baker, A, Seno, M, Lockett, S, Greer, YE, Rubin, JS, Salomon, DS & Bianco, C 2013, 'Cripto-1 enhances the canonical Wnt/β-catenin signaling pathway by binding to LRP5 and LRP6 co-receptors', Cellular Signalling, vol. 25, no. 1, pp. 178-189. https://doi.org/10.1016/j.cellsig.2012.09.024

Cripto-1 enhances the canonical Wnt/β-catenin signaling pathway by binding to LRP5 and LRP6 co-receptors. / Nagaoka, Tadahiro; Karasawa, Hideaki; Turbyville, Thomas; Rangel, Maria Cristina; Castro, Nadia P.; Gonzales, Monica; Baker, Alyson; Seno, Masaharu; Lockett, Stephen; Greer, Yoshimi E.; Rubin, Jeffrey S.; Salomon, David S.; Bianco, Caterina.

In: Cellular Signalling, Vol. 25, No. 1, 01.01.2013, p. 178-189.

Research output: Contribution to journalArticle

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AU - Nagaoka, Tadahiro

AU - Karasawa, Hideaki

AU - Turbyville, Thomas

AU - Rangel, Maria Cristina

AU - Castro, Nadia P.

AU - Gonzales, Monica

AU - Baker, Alyson

AU - Seno, Masaharu

AU - Lockett, Stephen

AU - Greer, Yoshimi E.

AU - Rubin, Jeffrey S.

AU - Salomon, David S.

AU - Bianco, Caterina

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