C/EBPδ demonstrates a dichotomous role in tumor initiation and promotion of epithelial carcinoma

Abstract

AbstractC/EBPδ(CEBPD), a gene part of the highly conserved basic-leucine zipper (b-ZIP) domain of transcriptional factors, is downregulated in 65% of high grade serous carcinoma of the ovary (HGSC). Overexpression ofC/EBPδin different tumors as glioblastoma and breast cancer either promotes tumor progression or inhibits growth. Despite these contradictory roles in different cancer types, we show thatC/EBPδoverexpression has a consistent function of downregulating proliferation and promoting migration in fallopian tube epithelial cells (FTE). We show that the FTE have both mesenchymal and epithelial cell characteristics. Further, our data supports a role forC/EBPδas an early regulatory transcriptional factor that promotes a mesenchymal to epithelial (MET) phenotype by upregulating E-cadherin and downregulating vimentin and N-cadherin in FTE cells. We demonstrate that overexpression ofC/EBPδin ovarian and breast cancer cell lines have consistent effects and phenotype as the FTE cells. Our findings suggest a role forC/EBPδin the early events of ovarian serous carcinogenesis which may be used to help further understand how the disease develops from a premalignant cells.