The AP-2alpha transcription factor regulates tumor cell migration and apoptosis

AP-2 proteins are a family of developmentally-regulated transcription factors. They are encoded by five different genes (alpha, beta, gamma, delta, and epsilon) but they share a common structure. AP-2 plays relevant roles in growth, differentiation, and adhesion by controlling the transcription of specific genes. Evidence shows that the AP-2 genes are involved in tumorigenesis and for instance, they act as tumor suppressors in melanomas and mammary carcinomas. Here we investigated the function of the AP-2alpha protein in cancer formation and progression focusing on apoptosis and migration. We introduced AP-2alpha-specific siRNA (as oligos or in retroviruses) in HeLa or MCF-7 human tumor cells and obtained a pronounced down-modulation of AP-2a mRNA and protein levels. In these cells, we observed a significant reduction of chemotherapy-induced apoptosis, migration, and motility and an increase in adhesion suggesting a major role of AP-2a during cancer treatment and progression (migration and invasion). We have data suggesting that migration is, at least in part, regulated by secreted factors. By performing a whole genome microarray analysis of the tumor cells expressing AP-2alpha siRNA, we identified several AP-2alpha-regulated genes involved in apoptosis and migration such as FAST kinase, osteopontin, caspase 9, members of the TNF family, laminin alpha 1, collagen type XII, alpha 1, and adam.