[The human E-cadherin/catenin complex: a potent invasion and tumor suppressor]

Cancer is a disease of the genome, evolving from phenotypically normal tissue to a benign non-invasive tumor, to an invasive tumor, and finally to metastasis. Tumor dissemination or metastasis in organs at a distance from the original tumor makes the disease mostly incurable. During this evolution, a number of genes, known as tumor suppressor genes, are inactivated, whereas a number of other genes, known as tumor promoter genes, are activated. Our research describes the E-cadherin/catenin complex as a potent inhibitor of cancer invasion. At least two elements of this complex, E-cadherin and (E-catenin, are encoded by a gene that meets the criteria of invasion and tumor suppressor genes. If both alleles of one of these genes disappear due to mutation or deletion, the tissue structure is no longer under control, which results in the penetration of tumor cells into other tissues. Originally, we regarded this complex merely as a physical mediator of cell-cell adhesion, a concept that would allow to explain the anti-invasive mechanism in a simple way. Later, however, the E-cadherin/catenin complex appeared to play also an important role as signal transducer. Moreover, we demonstrated inactivating mutations in the E-cadherin gene of a majority of invasive lobular breast cancers. Although this is not a general finding for all human carcinoma types, nearly all human forms of cancer accompanied with invasion show abnormalities of the E-cadherin/catenin complex. Hence, we considered it worthwhile to further study this complex and its still growing number of molecular interactions. Research focuses on genetic and posttranslational regulatory mechanisms of known and new elements of the complex, and explores the possibility of manipulation with therapeutic aims.