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B-cell translocation gene 2 (BTG2), a tumor suppressor gene, is downregulated in several types of human cancer cell. However, its function in skin cancer cells has not been fully elucidated. Therefore, the present study investigated the expression and function of BTG2 in skin cancer cells, and investigated the underlying molecular mechanism. The results indicated that BTG2 expression was downregulated in skin cancer cell lines. Overexpression of BTG2 significantly inhibited cell proliferation, cell cycle progression, and the invasion and migration of skin cancer cells. Furthermore, it was determined that overexpression of BTG2 significantly decreased the protein expression levels of β-catenin, cyclin D1 and v-myc avian myelocytomatosis viral oncogene homolog in skin cancer cells. This suggests that BTG2 may function as a tumor suppressor by interfering with the Wnt/β-catenin signaling pathway in skin cancer cells. Thus, novel therapeutic strategies and agents targeting BTG2 may be potential treatments for skin cancer. [ABSTRACT FROM AUTHOR]