title: The intracellular E-cadherin germline mutation V832 M lacks the ability to mediate cell-cell adhesion and to suppress invasion.
abstract: E-cadherin germline missense mutations have been shown to be responsible for significant loss of protein activity. A new cytoplasmic E-cadherin germline missense mutation (V832 M) was recently identified in a hereditary diffuse gastric cancer (HDGC) Japanese family. This E-cadherin mutant was cloned in a Chinese hamster ovary cell model system and functionally characterized, in terms of aggregation and invasion. Cells expressing the germline V832M mutant fail to aggregate and invade into collagen, supporting the pathogenic role of this germline missense mutation in gastric cancer. We also tested the ability of this mutation to activate the TCF-LEF trascriptional activity, in comparison with three other E-cadherin missense mutations (T340A, A634V and A617T), associated to loss of E-cadherin function. All the E-cadherin mutants reduced TCF-LEF activation to a similar extent as the wild-type protein, suggesting that the oncogenic effect of the E-cadherin mutants is unlikely to be transmitted through a beta-catenin-dependent activation of the WNT pathway.
authors.affiliation: Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), 4200 Porto, Portugal.
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Suriano
authors.forename: David
authors.initials: D
authors.lastname: Mulholland
authors.forename: Olivier
authors.initials: O
authors.lastname: de Wever
authors.forename: Paulo
authors.initials: P
authors.lastname: Ferreira
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Mateus
authors.forename: Eric
authors.initials: E
authors.lastname: Bruyneel
authors.forename: Colleen C
authors.initials: CC
authors.lastname: Nelson
authors.forename: Marc M
authors.initials: MM
authors.lastname: Mareel
authors.forename: Jun
authors.initials: J
authors.lastname: Yokota
authors.forename: David
authors.initials: D
authors.lastname: Huntsman
authors.forename: Raquel
authors.initials: R
authors.lastname: Seruca
mesh_terms: D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D018095:Germ-Line Mutation; D051821:Lymphoid Enhancer-Binding Factor 1; D011518:Proto-Oncogene Proteins / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
chemical_list: D015820:Cadherins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin