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them encode cell surface proteins, but some of them are protein kinases relaying signals from the cell surface, e.g. MEKK4.

For instance, KAI1 is a cell adhesion molecule encoded by a gene located on chromosome 11p12. Although this chromosomal region is subject to LOH in different carcinomas, the gene is never mutated or affected by promoter hypermethylation. Nevertheless, expression of KAI1 is down-regulated in many aggressive carcinomas.

Another gene in this category is CD9, which encodes a cell surface protein that sequesters EGF-like growth factors. Decreased expression of CD9 or KAI1 in primary tumors indicates a higher likelihood for the presence of metastases.

A more complex case is CD44. Like all proteins with the CD designation, it was first discovered as a lymphocyte surface antigen, but is expressed on many different cell types. It recognizes and binds to hyaluronic acid. In this fashion, it may function as an adhesion receptor directing lymphocytes to specific tissues. The CD44 gene is spliced in several alternative ways. As a consequence, altered expression in carcinomas may take the form of outright down-regulation with promoter hypermethylation or that of expression of CD44 variants that could contribute to the 'targeting' of metastatic cells.

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