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

33 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 - 01-2013

All Science Journal Classification (ASJC) codes

  • Cell Biology

Fingerprint Dive into the research topics of 'Cripto-1 enhances the canonical Wnt/β-catenin signaling pathway by binding to LRP5 and LRP6 co-receptors'. Together they form a unique fingerprint.

  • Cite this

    Nagaoka, T., Karasawa, H., Turbyville, T., Rangel, M. C., Castro, N. P., Gonzales, M., Baker, A., Seno, M., Lockett, S., Greer, Y. E., Rubin, J. S., Salomon, D. S., & Bianco, C. (2013). Cripto-1 enhances the canonical Wnt/β-catenin signaling pathway by binding to LRP5 and LRP6 co-receptors. Cellular Signalling, 25(1), 178-189. https://doi.org/10.1016/j.cellsig.2012.09.024