Tumour-associated E-cadherin mutations alter cellular morphology, decrease cellular adhesion and increase cellular motility.

摘要: A major function of the cell-to-cell adhesion molecule E-cadherin is maintenance cell and tissue integrity. deficiency in tumours leads to changes morphology motility, so that considered be a suppressor invasion. In this study we investigated functional consequences three tumour-associated gene mutations affect extracellular portion E-cadherin: in-frame deletions exons 8 or 9 point mutation exon 8, as they were found human gastric carcinomas. Human MDA-MB-435S breast carcinoma cells mouse L fibroblasts stably transfected with wild-type mutant cDNAs, resulting localization E-cadherin, morphology, strength calcium-dependent aggregation well motility actin cytoskeleton organization studied. We showed an epitheloid while all lines expressing exhibited more irregular shapes. Cells mutated most scattered appearance, whereas deletion had intermediate state. Mutant E-cadherins localized lateral regions contact sites. Additionally, both 8-mutated apical perinuclear localization, filaments drastically reduced. initial decreased and, remarkably, increased when was expressed. Therefore, conclude these may not simply but act trans-dominant-active manner, i.e. lead motility. Our suggests affecting are cause multiple morphological disorders could induce invasive behaviour diffuse type-gastric