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dc.contributor.authorSchwab, R.
dc.contributor.authorAmin, N.
dc.contributor.authorFlanagan, D.
dc.contributor.authorJohanson, T.
dc.contributor.authorPhesse, T.
dc.contributor.authorVincan, Elizabeth
dc.date.accessioned2017-07-27T05:21:25Z
dc.date.available2017-07-27T05:21:25Z
dc.date.created2017-07-26T11:11:26Z
dc.date.issued2017
dc.identifier.citationSchwab, 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.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/54558
dc.identifier.doi10.1002/dvdy.24527
dc.description.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.

dc.titleWnt is necessary for mesenchymal to epithelial transition in colorectal cancer cells
dc.typeJournal Article
dcterms.source.issn1058-8388
dcterms.source.titleDevelopmental Dynamics
curtin.departmentSchool of Biomedical Sciences
curtin.accessStatusFulltext not available


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