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.
|出版ステータス||Published - 1994 12月|
ASJC Scopus subject areas