Disease:Defects in CDH1 are a cause of gastric cancer [MIM:137215]; also known as hereditary familial diffuse gastric cancer (HDGC) . ,Disease:Defects in CDH1 are a cause of susceptibility to endometrial cancer [MIM:608089]. ,Disease:Defects in CDH1 are associated with ovarian cancer [MIM:167000]. Ovarian cancer is the leading cause of death from gynecologic malignancy. It is characterized by advanced presentation with loco-regional dissemination in the peritoneal cavity and the rare incidence of visceral metastases. These typical features relate to the biology of the disease , which is a principal determinant of outcome. ,Disease:Defects in CDH1 are involved in dysfunction of the cell-cell adhesion system , triggering cancer invasion (gastric , breast , ovary , endometrium and thyroid) and metastasis. ,Function:Cadherins are calcium dependent cell adhesion proteins. ,Function:Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. CDH1 is involved in mechanisms regulating cell-cell adhesions , mobility and proliferation of epithelial cells. Has a potent invasive suppressor role. It is a ligand for integrin alpha-E/beta-7. ,Function:E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta precursors. Has a strong inhibitory effect on APP C99 and C83 production. ,online information:E-cadherin entry ,PTM:During apoptosis or with calcium influx , cleaved by a membrane-bound metalloproteinase (ADAM10) , PS1/gamma-secretase and caspase-3 to produce fragments of about 38 kDa (E-CAD/CTF1) , 33 kDa (E-CAD/CTF2) and 29 kDa (E-CAD/CTF3) , respectively. Processing by the metalloproteinase , induced by calcium influx , causes disruption of cell-cell adhesion and the subsequent release of beta-catenin into the cytoplasm. The residual membrane-tethered cleavage product is rapidly degraded via an intracellular proteolytic pathway. Cleavage by caspase-3 releases the cytoplasmic tail resulting in disintegration of the actin microfilament system. The gamma-secretase-mediated cleavage promotes disaaaembly of adherens junctions. ,similarity:Contains 5 cadherin domains. ,subcellular location:Colocalizes with DLGAP5 at sites of cell-cell contact in intestinal epithelial cells. Anchored to actin microfilaments through association with alpha- , beta- and gamma-catenin. Sequential proteolysis induced by apoptosis or calcium influx , results in translocation from sites of cell-cell contact to the cytoplasm. ,subunit:Homodimer; disulfide-linked. Interacts directly , via the cytoplasmic domain , with CTNNB1 or JUP to form the PSEN1/cadherin/catenin adhesion complex which connects to the actin skeleton through the actin binding of alpha-catenin. Interaction with PSEN1 , cleaves CDH1 resulting in the disassociation of cadherin-based adherens junctions (CAJs) . Interacts with AJAP1 , CTNND1 and DLGAP5. ,tissue specificity:Non-neural epithelial tissues. ,
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