title: Wnt/FZD signaling and colorectal cancer morphogenesis.
abstract: 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.
authors.affiliation: Department of Pathology, University of Erlangen-Nürnberg, Krankenhausstr. 8-10, 91054 Erlangen, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Hlubek
authors.forename: Simone
authors.initials: S
authors.lastname: Spaderna
authors.forename: Otto
authors.initials: O
authors.lastname: Schmalhofer
authors.forename: Andreas
authors.initials: A
authors.lastname: Jung
authors.forename: Thomas
authors.initials: T
authors.lastname: Kirchner
authors.forename: Thomas
authors.initials: T
authors.lastname: Brabletz
mesh_terms: D002277:Carcinoma / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D051157:Frizzled Receptors / Q000378:metabolism*; D017491:Genes, APC; D006801:Humans; D009362:Neoplasm Metastasis; D015398:Signal Transduction; D051153:Wnt Proteins / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051157:Frizzled Receptors; D051153:Wnt Proteins; D051176:beta Catenin