APC senses cell-cell contacts and moves to the nucleus upon their disruption

Biochem Biophys Res Commun. 2001 Jun 22;284(4):982-6. doi: 10.1006/bbrc.2001.5066.

Abstract

The adenomatous polyposis coli (APC) tumor suppressor protein is involved in the Wnt/wingless pathway, modulating beta-catenin activity. We report the development of a highly specific, chemically synthesized oligobody (oligonucleotide-based synthetic antibody), directed against the N-terminal region of APC. Using this reagent, we found that within 16 h of disrupting HT-29 cell-cell contacts by harvesting cells with trypsin/EDTA treatment and replating, APC was translocated from the cytoplasm to the nucleus. Five days after plating the cells, when the cells had returned to their normal confluent phenotype and cell-cell contacts were reestablished, APC returned to the cytoplasm. These results suggest that APC functions as part of a "sensor" system, and responds to the loss of cell-cell contacts by moving to the nucleus, and returning to the cytoplasm when the contacts are fully restored.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli Protein
  • Antibodies
  • Antibodies, Monoclonal
  • Cell Communication / physiology*
  • Cell Nucleus / metabolism
  • Colonic Neoplasms
  • Cytoplasm / metabolism
  • Cytoskeletal Proteins / analysis
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Gene Library
  • Genes, APC*
  • Humans
  • Intercellular Junctions / physiology
  • Microscopy, Confocal
  • Oligodeoxyribonucleotides / chemistry
  • Protein Transport
  • Templates, Genetic
  • Tumor Cells, Cultured

Substances

  • Adenomatous Polyposis Coli Protein
  • Antibodies
  • Antibodies, Monoclonal
  • Cytoskeletal Proteins
  • Oligodeoxyribonucleotides