The alpha E-catenin gene (CTNNA1) acts as an invasion-suppressor gene in human colon cancer cells

The acquisition of invasiveness is a crucial step in the malignant progress ion of cancer. In cancers of the colon and of other organs the E-cadherin/c atenin complex, which is implicated in homotypic cell-cell adhesion as well as in signal transduction, serves as a powerful inhibitor of invasion. We show here that one allele of the alpha E-catenin (CTNNA1) gene is mutated i n the human colon cancer cell family HCT-8, which is identical to HCT-15, D LD-1 and HRT-18. Genetic instability, due to mutations in the HMSH6 (also c alled GTBP) mismatch repair gene, results in the spontaneous occurrence of invasive variants, all carrying either a mutation or exon skipping in the s econd alpha E-catenin allele, The alpha E-catenin gene is therefore, an inv asion-suppressor gene in accordance with the two-hit model of Knudsen for t umour-suppressor genes.