ZEB1 Directly Inhibits GPX4 Transcription Contributing to ROS Accumulation in Breast Cancer Cells

Abstract Prior studies have noted that Zinc finger E-box binding homeobox 1 (ZEB1) is a master transcription regulator, affecting the expression of nearly 2,000 genes in breast cancer cells, especially in epithelial-mesenchymal transition (EMT) process. In this study, we found that ZEB1 directly regulated Glutathione peroxidase 4 (GPX4) transcriptions, which was closely related to tumor reactive oxygen species (ROS) metabolism. We selected two human breast cancer cell linesMDA-MB-231 and MCF7 for ROS test, PCR, immunofluorescence, western blot, ChIP, luciferase assay and enzyme assay. The conclusions continue to be supported in mouse models and bioinformatics analysis. We found that ZEB1 directly bound to GPX4 promoter E-box motif (CANNTG) to inhibit GPX4 transcription, which contributing to ROS accumulation and tumorigenesis in breast cancer.