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

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

Research output: Contribution to journalReview article

9 Citations (Scopus)

Abstract

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
Volume24
Publication statusPublished - 1994
Externally publishedYes

Fingerprint

Catenins
Cadherins
Cell Adhesion
Neoplasms
Cell Line
Alleles
Mutation
Stomach Neoplasms
alpha Catenin
Genes
Carcinoma
Chromosomes, Human, Pair 16
Messenger RNA
beta Catenin
Point Mutation
Lung Neoplasms
Chromosomes
Breast Neoplasms
Amino Acids

Cite this

Kanai, Y., Oda, T., Shimoyama, Y., Ochiai, A., Oyama, T., Yoshiura, K., ... Hirohashi, S. (1994). Alterations of the cadherin-catenin cell adhesion system in cancers. Princess Takamatsu symposia, 24, 51-62.

Alterations of the cadherin-catenin cell adhesion system in cancers. / Kanai, Yae; Oda, T.; Shimoyama, Y.; Ochiai, A.; Oyama, T.; Yoshiura, K.; Akimoto, S.; Yamada, T.; Hirohashi, S.

In: Princess Takamatsu symposia, Vol. 24, 1994, p. 51-62.

Research output: Contribution to journalReview article

Kanai, Y, Oda, T, Shimoyama, Y, Ochiai, A, Oyama, T, Yoshiura, K, Akimoto, S, Yamada, T & Hirohashi, S 1994, 'Alterations of the cadherin-catenin cell adhesion system in cancers.', Princess Takamatsu symposia, vol. 24, pp. 51-62.
Kanai Y, Oda T, Shimoyama Y, Ochiai A, Oyama T, Yoshiura K et al. Alterations of the cadherin-catenin cell adhesion system in cancers. Princess Takamatsu symposia. 1994;24:51-62.
Kanai, Yae ; Oda, T. ; Shimoyama, Y. ; Ochiai, A. ; Oyama, T. ; Yoshiura, K. ; Akimoto, S. ; Yamada, T. ; Hirohashi, S. / Alterations of the cadherin-catenin cell adhesion system in cancers. In: Princess Takamatsu symposia. 1994 ; Vol. 24. pp. 51-62.
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