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

J Cell Sci. 2004 Jan 26;117(Pt 3):427-39. doi: 10.1242/jcs.00862. Epub 2003 Dec 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli Protein / chemistry
  • Adenomatous Polyposis Coli Protein / genetics
  • Adenomatous Polyposis Coli Protein / metabolism*
  • Adherens Junctions / metabolism
  • Cadherins / metabolism*
  • Cell Adhesion / physiology*
  • Cell Membrane / metabolism
  • Cell Movement / physiology*
  • Cell Nucleus / metabolism
  • Colonic Neoplasms / metabolism*
  • Cytoplasm / metabolism
  • Cytoskeletal Proteins / metabolism*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation
  • Humans
  • Lymphoid Enhancer-Binding Factor 1
  • Protein Transport
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism
  • Tumor Cells, Cultured
  • beta Catenin

Substances

  • Adenomatous Polyposis Coli Protein
  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Lymphoid Enhancer-Binding Factor 1
  • Trans-Activators
  • Transcription Factors
  • beta Catenin