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

Schwab, Renate H.M., Amin, Nancy, Flanagan, Dustin J., Johanson, Timothy M., Phesse, Toby ORCID: https://orcid.org/0000-0001-9568-4916 and Vincan, Elizabeth 2017. Wnt is necessary for mesenchymal to epithelial transition in colorectal cancer cells. Developmental Dynamics 247 (3) , pp. 521-530. 10.1002/dvdy.24527

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Abstract

Read the full text ePDF PDF ePDFPDF PDF Tools Share 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. Developmental Dynamics 247:521–530, 2018. © 2017 Wiley Periodicals, Inc.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher:	Wiley
ISSN:	1058-8388
Date of First Compliant Deposit:	26 May 2017
Date of Acceptance:	25 May 2017
Last Modified:	18 Nov 2024 13:45
URI:	https://orca.cardiff.ac.uk/id/eprint/100904

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