Patients with recessive dystrophic epidermolysis bullosa (RDEB) frequently present with squamous cell carcinomas (SCCs) probably as a result of chronic blistering and extensive scarring. These tumors are clinically aggressive as they metastasize readily. The metastasis-associated protein (MTA) -1, a transcription suppressor, is overexpressed in several epithelial neoplasms including SCCs. Our preliminary results demonstrate that MTA1 expression is induced by activation of the epidermal growth factor receptor (EGFR) As deregulation of EGFR signaling is frequently observed in aggressive epithelial neoplasms we propose to study the role of EGFR signaling and MTA1 expression in SCSCs derived in RDEB patients. Our Specific Aims are to establish cell lines derived from SCCs in non-RDEB and RDEB patients, characterize the malignant phenotype of these cells as it relates to EGFR expression and signaling and to expression of MTA1, examine the contribution of EGFR/MTA1 to proliferation, invasiveness, and cell survival and identify EGFR dependent signaling pathways contributing to MTA1 expression in these cells. The results from this research will provide invaluable tools for future analysis of the pathobiology of carcinoma cells and will ascertain whether EGFR/MTA1 signaling pathways contributes significantly to the metastasis and invasiveness of SCC derived from RDEB patients.