Density-dependent location and interactions of truncated APC and beta-catenin.
Adenomatous polyposis coli (APC) is a multifunctional tumour suppressor protein, central to development and the mature organism. It is mutated in most cases of colorectal cancer, rendering it ineffective in mediating beta-catenin degradation. We show that localization of full-length APC in colon carcinoma and noncancer cell lines is independent of cell density. However, the location of truncated APC is a function of cell density and in high-density cells truncated APC is predominantly not nuclear. Although the distribution of truncated APC and beta-catenin is closely linked in subconfluent SW480 cells, at high cell density they are not colocalized. We postulated that in this cell line this could be due to an increase in beta-catenin bound to E-cadherin with formation of adherens junctions at high cell density. However, while in coimmunoprecipitation assays we observe an increase in binding between beta-catenin and E-cadherin and a corresponding decrease in binding between beta-catenin and APC at high cell density, we did not observe a strict colocalization of beta-catenin and E-cadherin at the membrane of all cells.
Davies
Melanie L
ML
School of Biological Sciences, University of Wales Bangor, Deiniol Road, Bangor, Gwynedd LL57 2UW, UK.
Roberts
Gwyndaf T
GT
Spiller
David G
DG
Wakeman
Jane A
JA
D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D018613:Microscopy, Confocal; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D051176:beta Catenin; D000097606:Exportin 1 Protein
D025601:Adenomatous Polyposis Coli Protein; D003598:Cytoskeletal Proteins; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D051176:beta Catenin; D000097606:Exportin 1 Protein; C495270:CTNNB1 protein, human