Cadherin, mutated genes

The cadherins are calcium-dependent adhesion proteins that mediate direct cell-cell interactions.295 296 The external parts of the cadherins also have repeated structural domains with the Ig fold.297 298b They have high affinity for each other, allowing cadherins from two different cells to interact and tie the cells together with a zipper-like interaction that is stabilized by the bound Ca2+ ions,297 300 and may be relatively long-lived. The gene for cadherin E is often mutated in breast cancers and may be an important tumor suppressor gene (Box 11-D).301... 

Cadherins. Cadherins are a group of glycoproteins that facilitate Ca2+-dependent cell-cell adhesive interactions.20 When cadherin function is disrupted, the release of a tumor cell can result. It was shown that the aggressive metastasis of undifferentiated epithelial carcinoma cells that had lost cell-cell adhesion could be stopped by transfection with E-cad-herin cDNA.21 Therefore, it was suggested that E-cadherin suppresses metastasis,22 which was further supported by more recent studies that showed the loss of adhesion of human gastric, prostatic, and lung cancer cells was due to the gene mutation of a protein associated with the proper function of cadherin.23... 

Becker, K. R, Atkinson, M. J., Reich, U., Becker, I., Nekarda, H., Siewert, J. R. and Hoefler, H. (1995). E-cadherin gene mutations provide clues to diffuse type gastric carcinoma. Cancer Res. 54, 3845-3852. 

This chapter will focus on mutations in genes that code for proteins called APC, RAS, p53, and cadherin. RAS is pronounced "rass." The name "p53" arose because it is a protein (p) with a molecular weight of 53 kDa. These proteins have vital and useful functions In the... 

Kisinger, J., Berchuck, A., Koltler, M and Boyd, J. (1994), Mutations of the E-cadherin gene in human gynecologic cancers, l stnre Genet. 7, 98-102. 

The adhesion of cells to each other is normally due to interactions that involve a number of proteins of the extracellular matrix and the plasma membrane. Cadherin is a membrane-boimd protein. The N terminus of cadherin is extracellular. The N termini of cadherins sticking out of adjacent cells bind to each other. This interaction requires calcivun ions, hence the name Cadherin. An intracellular interaction is also required for adhesion to occur between cells. The C terminus of cadherin contacts the cytosol and binds to a protein called catenin (pronounced ca-TEE-nin). Catenin, in turn, binds to the cytoskeleton. The cytoskeleton is a network of proteins that crisscross about the plasma membrane and through the cell. Defects in the cadherin gene have been found in many samples of colorectal cancer. These mutations tend to occur in the N-terminal region, i.e., in the extracellular calcium-binding domain. 

Berx G, Cleton-Jansen AM, Nollet F, et al. E-cadherin is a tu-mour/invasion suppressor gene mutated in human lobular breast cancers. Embo J. 1995 14 6107-6115. 

The significance of cadherin-like proteins as receptors has been demonstrated by ectopic expression in different cell lines [12, 13] and is further corroborated by the presence of mutated cadherin genes in resistant Hdiothis virescens [14, 15] and Pectinophora gossypidla [16, 17] insect strains. In addition, glycolipids and glycosylated alkaline phosphatase have been implicated in Cry binding [18, 19]. 

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