title: Differences in the localization of the adenomatous polyposis coli-Asef/Asef2 complex between adenomatous polyposis coli wild-type and mutant cells.
abstract: The tumor suppressor adenomatous polyposis coli (APC) is mutated in familial adenomatous polyposis and in many sporadic colorectal tumors. Adenomatous polyposis coli is known to negatively regulate Wnt signaling by inducing the degradation of β-catenin. Adenomatous polyposis coli also interacts with the guanine nucleotide exchange factors Asef and Asef2 and stimulates their activity, thereby regulating cell adhesion and migration. Here we show that in confluent, non-motile MDCK II cells, Asef/Asef2 are colocalized with APC at the sites of cell-cell adhesion at the apical and junctional levels. In contrast, in colorectal tumor cells containing mutated APC, significant amounts of Asef/Asef2 and the truncated mutant APCs are localized mainly in the cytoplasm. These results suggest that localization of the Asef/Asef2-APC complex at the sites of cell-cell contact is critical for the regulation of cell adhesion, and that the aberrant subcellular localization of these complexes in colorectal tumor cells may contribute to the cell's aberrant adhesive and migratory properties.
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawasaki
authors.forename: Shiori
authors.initials: S
authors.lastname: Furukawa
authors.forename: Rina
authors.initials: R
authors.lastname: Sato
authors.forename: Tetsu
authors.initials: T
authors.lastname: Akiyama
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism / Q000502:physiology; D004285:Dogs; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D009154:Mutation
chemical_list: D020662:Guanine Nucleotide Exchange Factors
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