Relationship between the role of the adenomatous polyposis coli protein in colon cancer and its contribution to cytoskeletal regulation.
A unique feature of colon cancer is that truncation mutations in the APC (adenomatous polyposis coli) gene are common to most tumours. The high penetrance of APC mutations, especially in gut epithelium, supports the idea that APC may be involved in a number of the processes that govern the normal maintenance of this tissue: differentiation, migration, proliferation and apoptosis. Indeed, APC is involved in the regulation of beta-catenin and it also is an important regulator of the cytoskeleton. Thus mutations in APC lead to the accumulation of beta-catenin, which causes changes in differentiation, and they also produce changes in cytoskeletal organization, which results in altered cell migration and disrupted mitotic spindles. The function of APC in cytoskeletal organization is related to its effect on microtubules and F-actin. Depleting APC from cultured cells leads to changes in cytoskeletal organization. In addition, N-terminal fragments of APC, like those commonly found in tumours, compromise cell migration in Dictyostelium and in early developing chicken embryos. Consistent with the idea that such dominant effects are normally balanced by interactions within the full-length molecule, protein interactions of N-terminal fragments expressed in tumour cells can be altered by binding to C-terminal regions of APC commonly lost in tumours. This review summarizes effects of APC on the cytoskeleton and discusses how these functions of APC may contribute to its role in cancer.
Näthke
I
I
Cell and Developmental Biology, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK. inke@lifesci.dundee.ac.uk
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000782:Aneuploidy; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002642:Chick Embryo; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D003599:Cytoskeleton / Q000473:pathology*; D006801:Humans; D009154:Mutation
D025601:Adenomatous Polyposis Coli Protein