Work

TAZ/NRF2 positive feedback loop contributes to proliferation in bladder cancer through antagonistic ferroptosis

Year: 2025

Type: article

Abstract: Bladder cancer (BLCA) is a prevalent malignancy characterized by high recurrence and metastasis rates. Emerging evidence suggests that the NRF2-GPX4 axis is closely associated with ferroptosis. The transcriptional coactivator with PDZ-binding motif (TAZ) plays a crucial role in regulating ferroptosis; however, its role in BLCA remains unclear. In our study, we found that TAZ was markedly upregulated in BLCA tissues and BLCA cell lines. Gene set enrichment analysis indicated that TAZ depletion was related to ferroptosis and glutathione metabolism. Our results demonstrated that TAZ promotes the malignant progression of BLCA cells both in vitro and in vivo. Moreover, TAZ enhances NRF2 transcriptional activity through interaction with NRF2. We further revealed that TAZ-TEAD4 regulates NRF2 expression at the transcriptional level. Additionally, NRF2 regulates TAZ transcription by binding to its promoter region, establishing a positive feedback loop between TAZ and NRF2 that sustains GPX4 activation and inhibits ferroptosis in BLCA. These insights provide novel molecular targets for therapeutic treatment in BLCA.

Source: Cell Death Discovery

DOI: 10.1038/s41420-025-02506-9

Authors: Zhen Song, Shikai Gui, Xuepeng Rao, Gan Zhang, Yu Cheng, Tao Zeng

Institutions: Nanchang University, Second Affiliated Hospital of Nanchang University

Language: English

Topic: Ferroptosis and cancer prognosis

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,690