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

Yoshinori Ino, Masahiro Gotoh, Michiie Sakamoto, Kiyomi Tsukagoshi, Setsuo Hirohashi

Research output: Contribution to journalArticle

126 Citations (Scopus)

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 Ca2+-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.

Original languageEnglish
Pages (from-to)365-370
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number1
DOIs
Publication statusPublished - 2002 Jan 8

ASJC Scopus subject areas

  • General

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