Using fruitflies to help understand the molecular mechanisms of human hereditary diffuse gastric cancer

Mutations in the CDH1 gene, which encodes the cell adhesion molecule E-cadherin, are associated with hereditary diffuse gastric cancer in humans. Although most of the CDH1 mutations found are truncating, leading to non-functional E-cadherin, some are missense. These missense E-cadherin mutants result in full-length proteins which, when assayed in cell culture, still retain some biological activity. In order to understand the molecular causes of the malfunction of the E-cadherin missense forms found in patients, we developed a Drosophila model, where the effects of expressing the mutant forms can be studied in vivo (Pereira et al, 2006). Here, we review the results obtained so far, and outline possible ways of exploiting the fly model system to screen for pathways affected by specific E-cadherin missense mutant forms and to identify mechanisms that contribute to tumourigenesis.