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    Wnt is necessary for mesenchymal to epithelial transition in colorectal cancer cells

    Access Status
    Fulltext not available
    Authors
    Schwab, R.
    Amin, N.
    Flanagan, D.
    Johanson, T.
    Phesse, T.
    Vincan, Elizabeth
    Date
    2017
    Type
    Journal Article
    
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    Citation
    Schwab, R. and Amin, N. and Flanagan, D. and Johanson, T. and Phesse, T. and Vincan, E. 2017. Wnt is necessary for mesenchymal to epithelial transition in colorectal cancer cells. Developmental Dynamics. 247 (3): pp. 521-530.
    Source Title
    Developmental Dynamics
    DOI
    10.1002/dvdy.24527
    ISSN
    1058-8388
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/54558
    Collection
    • Curtin Research Publications
    Abstract

    Background: Metastasis underlies most colorectal cancer mortality. Cancer cells spread through the body as single cells or small clusters of cells that have an invasive, mesenchymal, nonproliferative phenotype. At the secondary site, they revert to a proliferative "tumor constructing" epithelial phenotype to rebuild a tumor. We previously developed a unique in vitro three-dimensional model, called LIM1863-Mph, which faithfully recapitulates these reversible transitions that underpin colorectal cancer metastasis. Wnt signaling plays a key role in these transitions and is initiated by the coupling of extracellular Wnt to Frizzled (FZD). Using the LIM1863-Mph model system we demonstrated that the Wnt receptor FZD7 is necessary for mesenchymal to epithelial transition (MET). Here we investigate the role of Wnt in MET. Results: Wnt secretion is dependent on palmitoylation by Porcupine (PORC). A PORC inhibitor (IWP2) that prevents Wnt secretion, blocked the epithelial transition of mesenchymal LIM1863-Mph cells. Wnt gene array analysis identified several Wnts that are upregulated in epithelial compared with mesenchymal LIM1863-Mph cells, suggesting these ligands in MET. Wnt2B was the most abundant differentially expressed Wnt gene. Indeed, recombinant Wnt2B could overcome the IWP2-mediated block in epithelial transition of mesenchymal LIM1863-Mph cells. Conclusions: Wnt2B co-operates with Frizzled7 to mediate MET in colorectal cancer.

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