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Updated: Nov 1, 2025
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
ZEB1 directly inhibits GPX4 transcription contributing to ROS accumulation in breast cancer cells
Xiao Han1, Xianxian Duan2, Zhanzhao Liu2
1State Key Laboratory of Medicinal Chemical Biology & College of Pharmacy, Nankai University, Tianjin, 300354, China.
Purpose:
Prior studies have noted that zinc finger E-box binding homeobox 1 (ZEB1) is a master transcription regulator, affecting the expression of nearly 2000 genes in breast cancer cells, especially in the epithelial-mesenchymal transition (EMT) process. We now tested the role of ZEB1 on the oxidative stress of cancer cells and explored its possible mechanisms.
Methods:
Two human breast cancer cell lines MDA-MB-231 and MCF7 were selected for the ROS test, PCR, immunofluorescence, Western blot, chromatin immunoprecipitation assay, luciferase assay, and enzyme assay. Mouse models experiments and bioinformatics analysis were conducted to test the indicated molecules.
Results:
We observed ZEB1 could inhibit GPX4 transcription by binding to the E-box motifs and promote breast cancer progression by accumulating intracellular ROS. From the perspective of ROS clearance, Vitamin E enhanced GPX4 function to consume L-glutathione and eliminated excess intracellular ROS.
Conclusions:
ZEB1 could not only regulate EMT, but also inhibit GPX4 transcription by binding to the E-box motif. It was important to note that the ZEB1/GPX4 axis had a therapeutic effect on breast cancer metabolism.
Insights
Zinc finger E-box binding homeobox 1 (ZEB1) inhibits GPX4 transcription, promoting breast cancer progression by increasing oxidative stress. Targeting the ZEB1/GPX4 axis offers a therapeutic strategy for breast cancer metabolism.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Zinc finger E-box binding homeobox 1 (ZEB1) is a key regulator of gene expression in breast cancer, particularly in epithelial-mesenchymal transition (EMT).
- The role of ZEB1 in regulating oxidative stress within cancer cells remains largely unexplored.
Purpose of the Study:
- To investigate the function of ZEB1 in oxidative stress in breast cancer cells.
- To elucidate the underlying molecular mechanisms by which ZEB1 influences oxidative stress and cancer progression.
Main Methods:
- Utilized human breast cancer cell lines (MDA-MB-231, MCF7) for ROS assays, PCR, immunofluorescence, Western blot, and chromatin immunoprecipitation.
- Conducted mouse model experiments and bioinformatics analysis to validate findings.
Main Results:
- ZEB1 was found to inhibit glutathione peroxidase 4 (GPX4) transcription by binding to E-box motifs.
- ZEB1 promotes breast cancer progression through the accumulation of intracellular reactive oxygen species (ROS).
- Vitamin E was observed to enhance GPX4 function, aiding in ROS clearance.
Conclusions:
- ZEB1 regulates EMT and inhibits GPX4 transcription via E-box binding.
- The ZEB1/GPX4 axis demonstrates therapeutic potential for modulating breast cancer metabolism.
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