Colorectal cancer cadherin

Dorudi, S., Hanby, A., Foulsom, R., STorthover,and Hart, I. (1995). Level of expression of E-cadherin mRhjA in colorectal cancer correlates with clinical outcome. Brii. J. Cancer 71, 614-616. 

Colorectal cancer involves the sequential accumulation of mutations in APC, p53, RAS, and possibly also in cadherin. The invasion of neighboring tissues occurs during one of the later steps in the life of the cancer cell. One of the properties of an invading cell is that it has lost its ability to adhere its sister cells (cell-to-cell adhesion). 

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. 

Hatakeyama, K. et al. (2004) Reduced expression of liver-intestine cadherin is associated with progression and lymph node metastasis of human colorectal carcinoma. Cancer Letters, 212 (2), 253-259. 

In MCF-7 breast cancer cells, yessotoxin caused the accumulation of an E-cadherin fragment [8]. This effect was seen with extremely low levels of the toxin, the EC50 being 0.55 nM. la-Homoyessotoxin was shown to be of similar activity, while 45-hydroxyyessotoxin, carboxy-yessotoxin, and noroxoyessotoxin were less effective [59]. In a later study [45], E-cadherin disruption was shown to occur not only in MCF-7 cells but also in Caco-2 cells from colorectal carcinoma and Madin Darby canine kidney cells. The effect was, however, specific for E-cadherin, since no fragments derived from N- or K-cadherin were found in cells exposed to yessotoxin [45]. 

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