Journal Article

E-cadherin germline missense mutations and cell phenotype: evidence for the independence of cell invasion on the motile capabilities of the cells

Gianpaolo Suriano, Maria José Oliveira, David Huntsman, Ana Rita Mateus, Paulo Ferreira, Fernando Casares, Carla Oliveira, Fátima Carneiro, José Carlos Machado, Marc Mareel and Raquel Seruca

in Human Molecular Genetics

Volume 12, issue 22, pages 3007-3016
Published in print November 2003 | ISSN: 0964-6906
Published online November 2003 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddg316
E-cadherin germline missense mutations and cell phenotype: evidence for the independence of cell invasion on the motile capabilities of the cells

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In Hereditary Diffuse Gastric Cancer syndrome, E-cadherin germline mutations of the missense type harbour significant functional consequences. In this study, we have characterised the effect of T340A, A617T, A634V and V832M E-cadherin germline missense mutations on cell morphology, motility and proliferation. Wild-type E-cadherin and A617T expressing cells have an epithelial-like morphology, with polarised cells migrating unidirectionally. T340A and A634V expressing cells, fibroblast-like, have a high motile phenotype. We show that this phenotype is dependent on an increased level of active RhoA. V832M expressing cells grow in piled-up structure of round cells, as an effect of the disturbance of the binding between α-catenin and β-catenin. The destabilisation of the adhesion complex is shown to hamper the motile capabilities of these cells. We did not observe any effect of the E-cadherin mutations on cell proliferation. We show the existence of a genotype–phenotype correlation between different E-cadherin mutations and cell behaviour. However, we demonstrate that the ability of cells expressing the different E-cadherin mutations to invade is independent on their motile capabilities, providing evidence that motility is neither necessary nor sufficient for cells to invade. Our data give new insights into the understanding of the mechanisms linking invasion and E-cadherin mutations in diffuse gastric cancer.

Journal Article.  6894 words.  Illustrated.

Subjects: Genetics and Genomics

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