A Truncated β-Catenin Disrupts the Interaction between E-Cadherin and α-Catenin

A Cause of Loss of Intercellular Adhesiveness in Human Cancer Cell Lines

Tsukasa Oyama, Yae Kanai, Atsushi Ochiai, Shingo Akimoto, Tatsuya Oda, Kazuyoshi Yanagihara, Akira Nagafuchi, Shoichiro Tsukita, Sayumi Shibamoto, Fumiaki Ito, Masatoshi Takeichi, Hikaru Matsuda, Setsuo Hirohashi

Research output: Contribution to journalArticle

277 Citations (Scopus)

Abstract

Cadherin cell adhesion molecules play an essential role in creating tight intercellular association and are considered to work as an invasion suppressor system of cancer cells. They form a molecular complex with catenins, a group of cytoplasmic proteins including α- and β-catenins. While α-catenin has been demonstrated to be crucial for cadherin (unction, the role of β-catenin is not yet fully understood. In this study, we analyzed the cadherin-catenin system in two human cell lines, HSC-39 and its putative subline HSC-40A, derived from a signet ring cell carcinoma of stomach. These cells grow as loose aggregates or single cells, suggesting that their cadherin system is not functional. In these cell lines, an identical 321-base pair in-frame mRNA deletion of β-catenin was identified; this led to a 107-amino-acid deletion in the NH2-terminal region of the protein. Southern blot analysis disclosed a homozygous deletion in part of the β-catenin gene. On the other hand, these cells expressed E-cadherin, α-catenin, and plakoglobin of normal size. Immunoprecipitation analyses showed that E-cadherin was coprecipitated with the mutated β-catenin but not with α-catenin, and antibodies against β-catenin did not copurify α-catenin. However, the recombinant fusion protein containing wild-type β-catenin precipitated α-catenin from these cells. These results suggest that the dysfunction of E-cadherin in these cell lines is due primarily to its failure to interact with α-catenin, and that this defect results from the mutation in β-catenin. Thus, it is most likely that the association between E-cadherin and α-catenin is mediated by β-catenin, and that this process is blocked by NH2-terminal deletion in β-catenin. These findings indicate that genetic abnormality of β-catenin is one of the mechanisms responsible for loosening of cell-cell contact, and may be involved in enhancement of tumor invasion in human cancers.

Original languageEnglish
Pages (from-to)6282-6287
Number of pages6
JournalCancer Research
Volume54
Issue number23
Publication statusPublished - 1994
Externally publishedYes

Fingerprint

Catenins
Adhesiveness
Cadherins
Cell Line
Neoplasms
gamma Catenin
Signet Ring Cell Carcinoma
Recombinant Fusion Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A Truncated β-Catenin Disrupts the Interaction between E-Cadherin and α-Catenin : A Cause of Loss of Intercellular Adhesiveness in Human Cancer Cell Lines. / Oyama, Tsukasa; Kanai, Yae; Ochiai, Atsushi; Akimoto, Shingo; Oda, Tatsuya; Yanagihara, Kazuyoshi; Nagafuchi, Akira; Tsukita, Shoichiro; Shibamoto, Sayumi; Ito, Fumiaki; Takeichi, Masatoshi; Matsuda, Hikaru; Hirohashi, Setsuo.

In: Cancer Research, Vol. 54, No. 23, 1994, p. 6282-6287.

Research output: Contribution to journalArticle

Oyama, T, Kanai, Y, Ochiai, A, Akimoto, S, Oda, T, Yanagihara, K, Nagafuchi, A, Tsukita, S, Shibamoto, S, Ito, F, Takeichi, M, Matsuda, H & Hirohashi, S 1994, 'A Truncated β-Catenin Disrupts the Interaction between E-Cadherin and α-Catenin: A Cause of Loss of Intercellular Adhesiveness in Human Cancer Cell Lines', Cancer Research, vol. 54, no. 23, pp. 6282-6287.
Oyama, Tsukasa ; Kanai, Yae ; Ochiai, Atsushi ; Akimoto, Shingo ; Oda, Tatsuya ; Yanagihara, Kazuyoshi ; Nagafuchi, Akira ; Tsukita, Shoichiro ; Shibamoto, Sayumi ; Ito, Fumiaki ; Takeichi, Masatoshi ; Matsuda, Hikaru ; Hirohashi, Setsuo. / A Truncated β-Catenin Disrupts the Interaction between E-Cadherin and α-Catenin : A Cause of Loss of Intercellular Adhesiveness in Human Cancer Cell Lines. In: Cancer Research. 1994 ; Vol. 54, No. 23. pp. 6282-6287.
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abstract = "Cadherin cell adhesion molecules play an essential role in creating tight intercellular association and are considered to work as an invasion suppressor system of cancer cells. They form a molecular complex with catenins, a group of cytoplasmic proteins including α- and β-catenins. While α-catenin has been demonstrated to be crucial for cadherin (unction, the role of β-catenin is not yet fully understood. In this study, we analyzed the cadherin-catenin system in two human cell lines, HSC-39 and its putative subline HSC-40A, derived from a signet ring cell carcinoma of stomach. These cells grow as loose aggregates or single cells, suggesting that their cadherin system is not functional. In these cell lines, an identical 321-base pair in-frame mRNA deletion of β-catenin was identified; this led to a 107-amino-acid deletion in the NH2-terminal region of the protein. Southern blot analysis disclosed a homozygous deletion in part of the β-catenin gene. On the other hand, these cells expressed E-cadherin, α-catenin, and plakoglobin of normal size. Immunoprecipitation analyses showed that E-cadherin was coprecipitated with the mutated β-catenin but not with α-catenin, and antibodies against β-catenin did not copurify α-catenin. However, the recombinant fusion protein containing wild-type β-catenin precipitated α-catenin from these cells. These results suggest that the dysfunction of E-cadherin in these cell lines is due primarily to its failure to interact with α-catenin, and that this defect results from the mutation in β-catenin. Thus, it is most likely that the association between E-cadherin and α-catenin is mediated by β-catenin, and that this process is blocked by NH2-terminal deletion in β-catenin. These findings indicate that genetic abnormality of β-catenin is one of the mechanisms responsible for loosening of cell-cell contact, and may be involved in enhancement of tumor invasion in human cancers.",
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AU - Oyama, Tsukasa

AU - Kanai, Yae

AU - Ochiai, Atsushi

AU - Akimoto, Shingo

AU - Oda, Tatsuya

AU - Yanagihara, Kazuyoshi

AU - Nagafuchi, Akira

AU - Tsukita, Shoichiro

AU - Shibamoto, Sayumi

AU - Ito, Fumiaki

AU - Takeichi, Masatoshi

AU - Matsuda, Hikaru

AU - Hirohashi, Setsuo

PY - 1994

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