GSE240039 Expression of PVRL4, a molecular target for cancer treatment, is transcriptionally regulated by FOS family protein [ATAC]

Contributors : Tomoyuki Nanamiya ; Kiyoko Takane ; Kiyoshi Yamaguchi ; Yoichi FurukawaSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensNectin-4 or PVRL4 is a promising therapeutic target because its augmented expression has been found in a wide range of human cancers. It is of note that Enfortumab Vedotin, an ADC for PVRL4 is clinically used for the treatment of urothelial bladder cancer. In addition, rMV-SLAMblind, a genetically engineered oncolytic measles virus, can infect cancer cells and induce apoptosis through an interaction with PVRL4. Although the transcripts of PVRL4 are elevated in breast, lung and ovarian cancer, the mechanism(s) of its overexpression has not been uncovered. To clarify the regulatory mechanism(s) of its elevated expression in breast cancer cells, we searched for its regulatory region(s) using ATAC-seq and ChIP-seq data. Using breast cancer cells, we identified an enhancer region. Additional analyses disclosed that FOS interacted with the enhancer region, and the alterations of the FOS-binding motifs decreased the reporter activity. Consistent with these data, exogenous expression of FOS enhanced not only the reporter activity but also PVRL4 expression in breast cancer cells. Furthermore, RNA-seq analysis using breast cancer cells treated with PVRL4-siRNA revealed its possible involvement in cytokine response and immune systems. These data suggest that FOS is involved, at least partly, in the ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research