Rel Family Transcription Factor NFAT5 Upregulates COX2 via HIF-1α Activity in Ishikawa and HEC1a Cells.
Toshiyuki OkumuraJanet P Raja XavierJana PasternakZhiqi YangCao HangBakhtiyor NosirovYogesh SinghJakob AdmardSara Yvonne BruckerStefan KommossSatoru TakedaAnnette StaeblerFlorian LangMadhuri S SalkerPublished in: International journal of molecular sciences (2024)
Nuclear factor of activated T cells 5 (NFAT5) and cyclooxygenase 2 (COX2; PTGS2 ) both participate in diverse pathologies including cancer progression. However, the biological role of the NFAT5-COX2 signaling pathway in human endometrial cancer has remained elusive. The present study explored whether NFAT5 is expressed in endometrial tumors and if NFAT5 participates in cancer progression. To gain insights into the underlying mechanisms, NFAT5 protein abundance in endometrial cancer tissue was visualized by immunohistochemistry and endometrial cancer cells (Ishikawa and HEC1a) were transfected with NFAT5 or with an empty plasmid. As a result, NFAT5 expression is more abundant in high-grade than in low-grade endometrial cancer tissue. RNA sequencing analysis of NFAT5 overexpression in Ishikawa cells upregulated 37 genes and downregulated 20 genes. Genes affected included cyclooxygenase 2 and hypoxia inducible factor 1α ( HIF1A ). NFAT5 transfection and/or treatment with HIF-1α stabilizer exerted a strong stimulating effect on HIF-1α promoter activity as well as COX2 expression level and prostaglandin E2 receptor (PGE2) levels. Our findings suggest that activation of NFAT5-HIF-1α-COX2 axis could promote endometrial cancer progression.
Keyphrases
- endometrial cancer
- nuclear factor
- toll like receptor
- low grade
- high grade
- transcription factor
- endothelial cells
- induced apoptosis
- signaling pathway
- poor prognosis
- genome wide
- gene expression
- epithelial mesenchymal transition
- dna methylation
- binding protein
- immune response
- young adults
- squamous cell carcinoma
- crispr cas
- inflammatory response
- small molecule
- lymph node metastasis
- microbial community
- long non coding rna
- replacement therapy
- dna binding
- anaerobic digestion
- squamous cell