Synergistic inhibition of TNBC by USP33 and TAP63 through autophagy and ferroptosis activation.

ABSTRACT:

Background

Triple-negative breast cancer (TNBC) is an aggressive malignancy lacking effective targeted therapies. Given the growing importance of regulated cell death pathways, we investigated the role of USP33 and its interaction with the tumor suppressor TAP63 in modulating ferroptosis and autophagy in TNBC.

Methods

An integrative approach combining bioinformatic screening, in vitro molecular and cellular assays, and in vivo xenograft models was employed to evaluate the USP33-TAP63 axis. Protein interaction and ubiquitination were assessed via co-immunoprecipitation and ubiquitin chain analysis. Ferroptosis and autophagy were monitored using fluorescence probes, electron microscopy, and key biomarkers. Statistical significance was assessed via Student's t-test and ANOVA.

SUBMITTER: Qu F 

PROVIDER: S-EPMC12350871 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature