SMAGP, a new small trans-membrane glycoprotein altered in cancer.

Using the Affymetrix array technology, we previously identified an EST strongly expressed in several metastatic cell lines. In the present study, we cloned the corresponding cDNA that encodes a new glycoprotein composed of 97 amino acids and containing a trans-membrane domain. Therefore, we named it SMAGP for Small trans-Membrane And Glycosylated Protein. SMAGP is strongly conserved during evolution. It is expressed by normal epithelia of various organs, the protein being notably localized to the lateral face of the plasma membrane of cohesive well-polarized epithelial cells. In addition, SMAGP contains binding domains for the protein 4.1 and the PDZ domain of MAGUK proteins. Similar protein features are observed in several cell-surface proteins involved via ternary complexes in intercellular processes leading to cytoskeleton assembly as well as intracellular signalling. Thus, SMAGP might similarly be involved in a scaffolding protein complex, and therefore participate in the epithelium organization or in subsequent functions. Immunohistochemical data obtained using human breast, colon and lung cancer samples sustain this hypothesis since they showed that, in both primary tumours and metastases, reduced expression and/or cytoplasmic redistribution of SMAGP is superimposable with low histological tumour differentiation features, namely a lack of epithelial cell polarity and disorganized tissue phenotype.