Abstract
The human E-cadherin gene CDH1 is located on chromosome 16q22.1. The 120 kDa glycoprotein encoded by CDH1 displays a large extracellular domain, a transmembrane segment and a short cytoplasmic domain. E-cadherin is located in regions of cell-cell contact known as adherens junctions, and it belongs to the family of genes encoding for the so-called calcium-dependent cell adhesion molecules. The N-terminal ends of the large extracellular domains of the dimers interact with similar E-cadherin dimers from the opposing cell surface, and the C-terminal ends of the cytoplasmic domains are associated with the catenins and the actin cytoskeleton. Adhesive contacts between cells provide a physical anchoring system that is necessary to form highly organized tissues. Also, these contacts allow for functional cross-talks between molecular components of the cell membrane and intracellular pathways. There is also evidence that cadherins are not only targets for signaling pathways that regulate adhesion, but may themselves send signals that regulate basic cellular processes, such as migration, proliferation, apoptosis and cell differentiation. Loss of E-cadherin function has been associated with malignant transformation and tumor progression. In fact, these malignant carcinoma cells are often characterized by poor intercellular adhesion, loss of the differentiated epithelial morphology, increased cellular motility and acquisition of epithelial-mesenchymal transition features. In human tumors, the loss of E-cadherin-mediated cell adhesion correlates with the loss of the epithelial morphology and with the acquisition of metastatic potential by the carcinoma cells. Thus, a tumor invasion/suppressor role has been assigned to this gene and this role is underscored by the observation that hereditary predisposition to gastric cancer results from germline mutations in CDH1.
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Abbreviations
- CAMs:
-
Cell Adhesion Molecules
- E:
-
Epithelial
- EGFR:
-
Epidermal Growth Factor Receptor
- EMT:
-
Epithelial Mesenchymal Transition
- RHOA:
-
Ras HOmolog gene family member A
- RTKs:
-
Receptor-type Tyrosine Kinases
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Graziano, F. (2013). The E-Cadherin Gene, Structure and Function. In: Corso, G., Roviello, F. (eds) Spotlight on Familial and Hereditary Gastric Cancer. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6570-2_4
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DOI: https://doi.org/10.1007/978-94-007-6570-2_4
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