title: Lack of adenomatous polyposis coli protein correlates with a decrease in cell migration and overall changes in microtubule stability.
abstract: Most sporadic colorectal tumors carry truncation mutations in the adenomatous polyposis coli (APC) gene. The APC protein is involved in many processes that govern gut tissue. In addition to its involvement in the regulation of beta-catenin, APC is a cytoskeletal regulator with direct and indirect effects on microtubules. Cancer-related truncation mutations lack direct and indirect binding sites for microtubules in APC, suggesting that loss of this function contributes to defects in APC-mutant cells. In this study, we show that loss of APC results in disappearance of cellular protrusions and decreased cell migration. These changes are accompanied by a decrease in overall microtubule stability and also by a decrease in posttranslationally modified microtubules in the cell periphery particularly the migrating edge. Consistent with the ability of APC to affect cell shape, the overexpression of APC in cells can induce cellular protrusions. These data demonstrate that cell migration and microtubule stability are linked to APC status, thereby revealing a weakness in APC-deficient cells with potential therapeutic implications.
authors.affiliation: Division of Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom.
authors.forename: Karin
authors.initials: K
authors.lastname: Kroboth
authors.forename: Ian P
authors.initials: IP
authors.lastname: Newton
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Kita
authors.forename: Dina
authors.initials: D
authors.lastname: Dikovskaya
authors.forename: Jürg
authors.initials: J
authors.lastname: Zumbrunn
authors.forename: Clare M
authors.initials: CM
authors.lastname: Waterman-Storer
authors.forename: Inke S
authors.initials: IS
authors.lastname: Näthke
mesh_terms: D000107:Acetylation; D025601:Adenomatous Polyposis Coli Protein / Q000737:chemistry / Q000172:deficiency*; D045744:Cell Line, Tumor; D002465:Cell Movement; D048430:Cell Shape; D022081:Cell Surface Extensions / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D008870:Microtubules / Q000378:metabolism*
chemical_list: D025601:Adenomatous Polyposis Coli Protein