Recent studies have found that EPS8, a mediator of growth factor signaling to the cytoskeleton, may upregulate expression of the FoxM1B transcription factor and aurora A kinase, both of which have been linked to oncogenic activity. Cell lines transfected with EPS8 and FoxM1B, and appropriate controls, were generated and analyzed by MTT proliferation assays and flow cytometry for relative rates of cell proliferation as well as to determine the percentage of cells in different phases of the cell cycle. qRT-PCR and western blots confirmed higher levels of EPS8, FoxM1B and Aurora A kinase in the overexpressing cell lines. To investigate the role of PI3K-dependent signaling in EPS8-mediated upregulation of FoxM1B and its targets, studies were carried out usingLY294002, an inhibitor of PI3K. In cells overexpressing EPS8, treatment with LY294002resulted in decreased expression of FoxM1B and Aurora A kinase, indicating that PI3Ksignaling mediates EPS8-dependent upregulation of FoxM1B and Aurora A kinase. The study suggests that EPS8 deregulates cell growth by affecting the expression of common regulators of cell cycle progression, in part through PI3K, a known pro-oncogenic kinase.