Investigation of Psoriasin (S100A7) and its role in a vb 6 - Dependent Invasion

Integrins are heterodimeric, transmembrane proteins that-act as cell surface receptors for extracellular matrix components and which have been implicated in a variety of cell processes including adhesion, migration, and proliferation. Specifically, avB6 integrin is expressed only by epithelial cells and then only during tissue remodelling events including foetal development, wound healing, inflammation and ~arcinoma formation. In this latter event upregula~ed a:vB6 expression is .seen particularly in squamous cell carcinoma of the skin and the mouth. The B6 subunit contains an unique 11 amino acid extension at its C-terminus (EKQKVDLSTDC), which our laboratory has shown to be essential, and sufficient, for promoting the invasive activity of carcinoma cells. To attempt to understand the mechanism behind this phenomenon, I initiated a search for molecules that bind specifically to these Cterminal 11 amino acids. GST -chimeras of either the B6 full length tail or C-terminus truncated-tail were generated for use in pull-down assays. Resulting complexes were subjected to 2D electrophoresis and proteomics analysis to reveal differentially associated proteins. Results identified the S 100 protein, psoriasin (SIOOA 7), as a novel binding partner to the C-terminal 11 amino acids of B6 integrin. Using siRNA mediated downregulation of psoriasin, this study. shows that psoriasin is required for the migratory, but not the adhesive, functions of avB6; a result replicating the phenotype of oral see cells lacking the unique B6 C-terminus. Moreover, psoriasin is shown to be necessary for avB6-dependent invasion of both oral and breast carcinoma cell lines and investigation of possible mechanisms which underlie these observations has identified a possible novel (36 signalling pathway.EThOS - Electronic Theses Online ServiceGBUnited Kingdo