Alterations of the cadherin-catenin cell adhesion system in cancers.

Y. Kanai, T. Oda, Y. Shimoyama, A. Ochiai, T. Oyama, K. Yoshiura, S. Akimoto, T. Yamada, S. Hirohashi

Research output: Contribution to journalReview articlepeer-review

9 Citations (Scopus)


The E-cadherin-mediated cell adhesion system acts as an "invasion suppressor" system, which is widely considered to be inactivated when the expression of E-cadherin is reduced and/or heterogeneous. To further investigate the molecular mechanisms responsible for dysfunction of this system in cancers, we examined human carcinoma cell lines lacking tight cell-cell adhesion. In KATO-III, established from stomach cancer, a point mutation of the E-cadherin gene resulted in a mRNA splicing error and markedly reduced E-cadherin expression. In another stomach cancer cell line, MKN 45, an 18-bp deletion of the E-cadherin gene caused a mRNA splicing error and a 4-amino-acid deletion, which was considered to alter the conformation around the key Ca(2+)-binding motif. In these two cell lines, the wild-type allele of the E-cadherin locus, which was assigned to chromosome 16q, was lost. Also in vivo, we found mutation of E-cadherin in breast cancers, where allele loss on chromosome 16 has frequently been reported. Thus, dysfunction of E-cadherin could be caused by a combination of the loss of one allele and a mutation in the remaining allele. Homologous deletion of part of the alpha-catenin gene, resulting in markedly reduced expression, was observed in a human lung cancer cell line, PC9. Recently, we also found mutations of beta-catenin in human carcinoma cell lines. These findings indicate the possible involvement of genetic abnormalities of various components in inactivation of the E-cadherin-mediated "invasion suppressor system" in cancers.

Original languageEnglish
Pages (from-to)51-62
Number of pages12
JournalPrincess Takamatsu symposia
Publication statusPublished - 1994
Externally publishedYes


Dive into the research topics of 'Alterations of the cadherin-catenin cell adhesion system in cancers.'. Together they form a unique fingerprint.

Cite this