Dysadherin, a cancer-associated cell membrane glycoprotein, down-regulates E-cadherin and promotes metastasis

Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):365-70. doi: 10.1073/pnas.012425299. Epub 2001 Dec 26.

Abstract

We report the cloning and characterization of a cancer-associated cell membrane glycoprotein recognized by mAb NCC-3G10. The antibody showed strong reactivity to a wide variety of cancer cells, but only to a limited number of normal cells including lymphocytes, endothelial cells, and basal cells of stratified squamous epithelium. The cDNA for the antigen encodes 178 aa, which includes a putative signal sequence, a potential O-glycosylated extracellular domain, a single transmembrane domain, and a short cytoplasmic tail. Transfection of the cDNA into PLC/PRF/5 liver cancer cells resulted in reduced cell-cell adhesiveness, based on both morphology and results of Ca(2+)-dependent cell aggregation assay. In transfected cells, E-cadherin was markedly decreased at the protein level in inverse proportion to the expression level of the antigen recognized by NCC-3G10, but not at the mRNA level. Aggregation of the antigen by NCC-3G10-coated beads triggered accumulation of actin, suggesting some interplay between this antigen and E-cadherin through actin. When metastatic ability was examined in severe combined immunodeficient mice by injecting PLC/PRF/5 cells into the spleen, the transfectants formed a markedly higher number of metastatic nodules in comparison with controls. We have named this cell membrane glycoprotein, which down-regulates E-cadherin and promotes metastasis, dysadherin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Amino Acid Sequence
  • Antibodies, Monoclonal / metabolism
  • Base Sequence
  • Blotting, Northern
  • Blotting, Western
  • Cadherins / metabolism*
  • Calcium / metabolism
  • Cell Line
  • Cloning, Molecular
  • DNA, Complementary / metabolism
  • Down-Regulation*
  • Glycoproteins / metabolism*
  • Glycosylation
  • Humans
  • Immunohistochemistry
  • Liver / pathology
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / genetics*
  • Microscopy, Electron
  • Molecular Sequence Data
  • Neoplasm Metastasis
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / chemistry*
  • Neoplasm Proteins / genetics*
  • Neoplasms / metabolism*
  • Open Reading Frames
  • Protein Structure, Tertiary
  • RNA, Messenger / metabolism
  • Sequence Homology, Amino Acid
  • Time Factors
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Actins
  • Antibodies, Monoclonal
  • Cadherins
  • DNA, Complementary
  • FXYD5 protein, human
  • Glycoproteins
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • RNA, Messenger
  • Calcium

Associated data

  • GENBANK/AB072911