Multi-omics profiling reveals key signaling pathways in ovarian cancer controlled by STAT3

Inhibiting STAT3 signaling reduces tumor progression, metastasis and chemoresistance, however the precise molecular mechanism has not been fully delineated in ovarian cancer. In this study, we generated knockout (KO) ovarian cancer cell lines. Effects of KO on cell proliferation, migration and spheroid formation were assessed and effects on tumor growth were tested using several tumor xenograft models. We used multi-omic genome-wide profiling to identify multi-level (Bru-Seq, RNA-Seq, and MS Proteomic) expression signatures of KO ovarian cancer cells. We observed that deletion of blocked cell proliferation and migration and suppressed tumor growth in mice. Deletion of transcriptionally suppressed key genes involved in EMT, cell cycle progression, E2F signaling, and altered stemness markers. Notably, KO of resulted in modulation of the expression of other STAT family members. Our study presents a rich, multi-faceted summary of the molecular mechanisms impacted by deletion and provides new insight for 's potential as a therapeutic target in ovarian cancer.