IFN induces Bcl3 expression by JAK1/STAT1/p65 signaling, resulting in increased IL-8 expression in ovarian cancer cells

We have recently shown that IFN?, produced during cancer therapy, induces expression of the Bcl3 proto-oncogene in ovarian cancer (OC) cells, resulting in their increased proliferation, migration, and invasion, but the mechanisms are unknown. Here, we demonstrate that the IFN?-induced Bcl3 expression is dependent on JAK1 and STAT1 signaling, and on p65 NF?B. Furthermore, the IFN?-induced Bcl3 expression is associated with an increased occupancy of Ser-727 phosphorylated STAT1 and acetylated histone H3 at the Bcl3 promoter. Our data indicate that Bcl3 promotes expression of the pro-inflammatory chemokine interleukin-8 (IL-8) in OC cells. These findings identify Bcl3 as a novel target of IFN?/JAK1/STAT1 signaling and suggest that targeting the JAK1/STAT1 pathway may suppress IFN?-induced Bcl3 expression in OC.