Expression of PVRL4, a molecular target for cancer treatment, is transcriptionally regulated by FOS

• DOI: 10.3892/or.2023.8676
• Publication Date: 2023-12-05T07:45:19Z
• Authors: Tomoyuki Nanamiya; Kiyoko Takane; Kiyoshi Yamaguchi; Yuya Okawara; Mariko Arakawa; Akari Saku; Tsuneo Ikenoue; Tomoko Fujiyuki; Misako Yoneda; Chieko Kai; Yoichi Furukawa
• Keywords: Chromatin immunoprecipitation

PVRL4 (or nectin‑4) is a promising therapeutic target since its upregulated expression found in wide range of human cancer types. Enfortumab vedotin, an antibody‑drug conjugate targeting PVRL4, clinically used for the treatment urothelial bladder cancer. In addition, rMV‑SLAMblind, genetically engineered oncolytic measles virus, can infect cells and induce apoptosis through interaction with PVRL4. Although <em>PVRL4</em> transcript levels are elevated breast, lung ovarian cancer, mechanisms upregulation have not yet been uncovered. To clarify regulatory breast cells, Assay Transposase‑Accessible Chromatin‑sequencing chromatin immunoprecipitation‑sequencing (ChIP‑seq) data were to search regions. Using enhancer region was ultimately identified. Additional analyses, including ChIP reporter assays, demonstrated that FOS interacted region, alterations FOS‑binding motifs decreased activity. Consistent these data, exogenous <em>FOS</em> enhanced activity cells. Furthermore, RNA‑seq analysis using treated small interfering RNA revealed possible involvement cytokine response immune system. These suggested involved, at least partly, regulation may regulate cytokines