BORIS Expression in Ovarian Cancer Precursor Cells Alters the CTCF Cistrome and Enhances Invasiveness through GALNT14

High-grade serous carcinoma (HGSC) is the most aggressive and predominant form of epithelial ovarian cancer and the leading cause of gynecologic cancer-related death. We have previously shown that (also known as , rother f the egulator of mprinted ites) is expressed in most ovarian cancers, and is associated with global and promoter-specific DNA hypomethylation, advanced tumor stage, and poor prognosis. To explore its role in HGSC, we expressed in human fallopian tube secretory epithelial cells (FTSEC), the presumptive cells of origin for HGSC. -expressing cells exhibited increased motility and invasion, and expression was associated with alterations in several cancer-associated gene expression networks, including fatty acid metabolism, TNF signaling, cell migration, and ECM-receptor interactions. Importantly, , a glycosyltransferase gene implicated in cancer cell migration and invasion, was highly induced by BORIS, and knockdown significantly abrogated BORIS-induced cell motility and invasion. In addition, analyses provided evidence for and coexpression in several cancers. Finally, ChIP-seq demonstrated that expression of was associated with and enhanced binding of CTCF at hundreds of loci, many of which correlated with activation of transcription at target genes, including . Taken together, our data indicate that may promote cell motility and invasion in HGSC via upregulation of , and suggests as a potential therapeutic target in this malignancy. IMPLICATIONS: These studies provide evidence that aberrant expression of BORIS may play a role in the progression to HGSC by enhancing the migratory and invasive properties of FTSEC.