E-cadherin

Cadherins are a superfamily of Ca2+-sensitive cell-cell adhesion molecules, which cause homophilic cell interactions. Cadherins can be divided into different subfamilies, namely, classical cadherins, desmosomal cadherins, protocadherins, and nonconventional cadherins (7TM cadherins, T-cadherin, FAT). Classical cadherins are often denoted by a prefix reflecting their principal expression domains e.g., E is epithelial, N is neuronal, and P is placental. However, this classification is not stringent, as for instance E-cadherin can also be found in certain neuronal tissues, and N-cadherin is also found in epithelial cells. Among the desmosomal cadherins, two subfamilies can be distinguished the desmocollins 1-3 and the desmogleins 1-4. 

Classical and desmosomal cadherins are constituents of different types of intercellular junctions. E-cadherin, the classical cadherin of epithelial cells, is part of the adherens junction (zonula adherens), which is attached to a belt of actin via the catenins. As the name says, desmosomal cadherins are part of the desmosomes, which are rivet-like structures that make focal connections between cells. Desmosomes are characterized by a... 

Fujita Y, Krause G, Scheffner M et al (2002) Hakai, a c-Cbl-like protein, ubiquitinates and induces endo-cytosis of the E-cadherin complex. Nat Cell Biol 4(3) 222-231... 

Carter, O., Bailey, G.S., and Dashwood, R.H., The dietary phytochemical chlorophyllin alters E-cadherin and P-catenin expression in human colon cancer cells International Research Conference on Food, Nutrition and Cancer, J. Nutr., 134,3441S, 2004. 

Lutz, K.L. Szabo,L. A. Thompson, D.L. Siahaan, T. J., Antibody recognition of peptide sequence from the cell-cell adhesion proteins N- and E-cadherins, Peptide Res. 9, 233-239 (1996). 

WJ Nelson, EM Shore, AZ Wang, RW Hammerton. (1990). Identification of a membrane-cytoskeletal complex containing the cell adhesion molecule uvomorulin (E-cadherin), ankyrin, and fodrin in Madin-Darby canine kidney epithehal cells. J Cell Biol 110 349-357. 

Figure 8.2 Design of protein-embedding barcode is depicted in (a) five thin layers of matrix (the thicker lines) coated with variable concentration of tested protein (thinner lines located above the matrix), (b) A FFPE tissue section of bladder cancer IHC-stained by monoclonal antibody to E-cadherine showing variable intensity of positive staining results which is compared with a protein-embedding bar code as designed in this chapter. Using computer-assisted image analysis with a special software, an automatic quantitative measurement of protein is performed. See color insert.

Blechschmidt K, Kremmer E, Hollweck R, et al. The E-cadherin repressor snail plays a role in tumor progression of endometrioid adenocarcinomas. Diagn. Mol. Pathol. 2007 16 222-228. 

Hipp S, Walch A, Schuster T, et al. Precise measurement of the E-cadherin repressor Snail in formalin-fixed endometrial carcinoma using protein lysate microarrays. Clin. Exp. Metastasis 2008 25 679-683. 

The classic cadherins are homophilic adhesion molecules. That is, E-cadherin expressed on one cell surface binds to E-cadherin expressed on an apposed cell surface, N-cadherin binds to N, P to P and so forth. It was originally thought that all cadherins would behave completely homophilically but it is now clear that, for example, N-cadherin can bind to R-cadherin, although perhaps more weakly than it would to N-cadherin. 

Fannon,A.M.,Sherman,D.L.,Ilyina-Gragerova,G.,Brophy, P. J., Friedrich, V. L. Jr and Colman, D. R. Novel E-cadherin mediated adhesion in peripheral nerve Schwann cell architecture is stabilized by intracellular signals elicited by autotypic adherens junctions. J. Cell Biol. 129 189-202, 1995. 

Unlike the situation with the integrins discussed earlier, it is loss of cadherin E that promotes metastasis. The evidence linking loss or decreased expression of cadherin E with cancer spread is as follows (M2). Firstly, a negative correlation exists between the expression of cadherin E and invasion for many different cancer cell lines. Secondly, in cell lines lacking cadherin E, invasion could be prevented by transfection with cDNA for this cadherin. Thirdly, reduction in cadherin E mRNA levels by antisense sequences induced the invasive phenotype in E-cadherin positive cells. Fourthly, antibodies inactivating cadherin E induced the invasive phenotype. These combined experiments are strong evidence that loss of cadherin E is associated with development of invasive phenotype and furthermore suggests that this adhesion molecule may be a suppressor of metastasis. 

Alveolar epithelial cells (AECs) are connected with each other by various epithelial cell-cell contacts (i.e., tight junctions, adherens junctions and others). These contacts comprise several groups of proteins, such as occludin, zonula occludens (ZO-1, -2, -3), claudins, tricellulin, E-cadherin and intercellular adhesion molecule-1 (ICAM-1) [13-15], Their regulation and interplay, which has influence on epithelial barrier properties, however, is largely unknown to date. 

Mengaud, J., Ohayon, H., Gounon, P., Mege, R.-M., and Cossart, P. (1996). E-cadherin is the receptor for intemalin, a surface protein required for entry of L. monocytogenes into epithelial cells. Cell 84, 923-932. 

It has been shown that IFN-y induces Fas on keratinocytes which renders them susceptible to apoptosis induction by infiltrating FasL+ T cells. This has been interpreted as an important event in eczema, mainly in atopic dermatitis. There is further evidence that cleavage of E-cadherin and sustained desmosomal cadherin contacts between keratinocytes that are undergoing apoptosis result in spon-gioform morphology in the epidermis as a hallmark of eczematous lesions. Suppression of keratinocyte activation and apoptosis thus remains a potential target for the treatment of atopic dermatitis [2]. 

Osada T, Sakamoto M, Ino Y, Iwamatsu A, Matsuno Y, Muto T et al (1996). E-cadherin is involved in the intrahepatic metastasis of hepatocellular carcinoma. Hepatology 24 1460-1467. 

Initially characterized as an autoantigen in a human connective tissue disease [62]. May be associated with methylation induced gene silencing and heterochromatin [64,65,103]. Interacts with a component of DNA repair machinery [308]. Functions in estrogen dependent repression of Snail. Aberrant Snail expression results in loss of expression of the cell adhesion molecule E-cadherin, an event associated with invasive growth of breast cancers [309]. 

Armicotte, J.S., lankova, 1., Miard, S., Fritz, V., Sarruf, D., Abella, A., Berthe, M.L., Noel, D., Pillon, A., Iborra, F., Dubus, P., Maudelonde, T., Culine, S. and Fajas, L. (2006) Peroxisome proliferator-activated receptor gamma regulates E-cadherin expression and inhibits growth and invasion of prostate cancer. Molecular and Cellular Biology, 26, 7561-7574. 

Green SK, Francia G, Isidore C et al (2004) Antiadhesive antibodies targeting E-cadherin sensitize multicellular tumor spheroids to chemotherapy in vitro. Mol Cancer Ther 3 149-159... 

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