IMR Press / FBL / Volume 12 / Issue 2 / DOI: 10.2741/2075

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Wnt/FZD signaling and colorectal cancer morphogenesis
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1 Department of Pathology, University of Erlangen-Nürnberg, Krankenhausstr. 8-10, 91054 Erlangen, Germany
Academic Editor:Elizabeth Vincan
Front. Biosci. (Landmark Ed) 2007, 12(2), 458–470;
Published: 1 January 2007
(This article belongs to the Special Issue WntFZD signalling in cancer and disease)

Malignant progression of colorectal carcinomas is characterized by an epithelial-mesenchymal transition (EMT)-like de-differentiation of the invading tumor cells. However a re-differentiation towards an epithelial phenotype, resembling a mesenchymal-epithelial transition (MET), is detectable in metastases. This indicates that malignant progression is based on dynamic processes, which can not be explained solely by irreversible genetic alterations, but must be additionally regulated by the tumor environment. The main oncoprotein in colorectal cancer is the Wnt-pathway effector beta-catenin, which in most cases is overexpressed due to mutations in the adenomatous polyposis coli (APC) tumor suppressor. EMT of tumor cells is associated with a nuclear accumulation of the transcriptional activator beta-catenin, which is reversed in metastases. Nuclear beta-catenin is involved in two fundamental processes in embryonic development: EMT and stem cell formation. Accumulating data demonstrate that aberrant nuclear expression of beta-catenin can also confer these two abilities to tumor cells, indicating the crucial role of aberrant Wnt-signaling for malignant tumor progression.

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