GSE131931
Ectopic CTCFL/BORIS expression in ovarian cancer precursor cells enhances cellular motility and invasion through GALNT14 and alters CTCF chromatin occupancy
High-grade serous carcinoma (HGSC) is the most aggressive and predominant form of epithelial ovarian cancer and the leading cause of gynecological cancer death. We have previously shown that CTCFL (also known as BORIS, Brother of the Regulator of Imprinted Sites) is expressed in a large proportion of ovarian cancers, which is associated with global and promoter-specific DNA hypomethylation, advanced tumor stage, and poor prognosis. To explore its functional role in HGSC, we expressed BORIS in human fallopian tube secretory epithelial cells (FTSEC), the presumptive cell of origin for HGSC. BORIS-expressing cells exhibited increased motility and invasion, and BORIS 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, GALNT14, a glycosyltransferase gene previously implicated in cancer cell migration and invasion, was highly induced by BORIS, and GALNT14 knockdown significantly abrogated BORIS-induced cell motility and invasion.  In addition, in silico analyses provided evidence for BORIS and GALNT14 co-expression in several human cancers.  Finally, ChIP-seq demonstrated that expression of BORIS in FTSEC cells was associated with de novo and enhanced binding of CTCF at hundreds of loci, many of which correlated with activation of transcription at target genes, including GALNT14. Taken together, our data indicate that BORIS may promote cell motility and invasion in HGSC via upregulation of GALNT14, and suggests BORIS as a potential therapeutic target in this malignancy. Overall design: Genome-wide mapping of CTCF and BORIS occupancy in FT282 cells ectopically expressed either EV (Empty Vector) or BORIS. Expression profiling by high throughput sequencing (RNA-seq) of FT282 cells ectopically expressed either EV (Empty Vector) or BORIS.