Restoration of full-length adenomatous polyposis coli (APC) protein in a colon cancer cell line enhances cell adhesion

Faux, MC; Ross, JL; Meeker, C; Johns, T; Ji, H; Simpson, RJ; Layton, MJ; Burgess, AW

Author(s): Faux, MC; Ross, JL; Meeker, C; Johns, T; Ji, H; Simpson, RJ; Layton, MJ; Burgess, AW;
Details: Publication Year 2004-01-26,Volume 117,Issue #3,Page 427-439
Journal Title: JOURNAL OF CELL SCIENCE
Publication Type: Journal Article
Abstract: The APC tumour suppressor gene is mutated in most colon cancers. A major role of APC is the downregulation of the beta-catenin/T-cell factor (Tcf)/lymphoid enhancer factor (LEF) signalling pathway; however, there are also suggestions that it plays a role in the organization of the cytoskeleton, and in cell adhesion and migration. For the first time, we have achieved stable expression of wild-type APC in SW480 colon cancer cells, which normally express a truncated form of APC. The ectopically expressed APC is functional, and results in the translocation of beta-catenin from the nucleus and cytoplasm to the cell periphery, and reduces beta-catenin/Tcf/LEF transcriptional signalling. E-cadherin is also translocated to the cell membrane, where it forms functional adherens junctions. Total cellular levels of E-cadherin are increased in the SW480APC cells and the altered charge distribution in the presence of full-length APC suggests that APC is involved in post-translational regulation of E-cadherin localization. Changes in the location of adherens junction proteins are associated with tighter cell-cell adhesion in SW480APC cells, with consequent changes in cell morphology, the actin cytoskeleton and cell migration in a wound assay. SW480APC cells have a reduced proliferation rate, a reduced ability to form colonies in soft agar and do not grow tumours in a xenograft mouse tumour model. By regulating the intracellular transport of junctional proteins, we propose that APC plays a role in cell adhesion in addition to its known role in beta-catenin transcriptional signalling.
Publisher: COMPANY OF BIOLOGISTS LTD
Keywords: TUMOR-SUPPRESSOR PROTEIN; BETA-CATENIN; E-CADHERIN; COLORECTAL-CANCER; EPITHELIAL-CELLS; MIN MICE; C-MYC; GENE; EXPRESSION; COMPLEX
Publisher's Version: https://doi.org/10.1242/jcs.00862
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2004-01-26 12:00:00