Deubiquitylase USP52 Promotes Bladder Cancer Progression by Modulating Ferroptosis through Stabilizing SLC7A11/xCT.

ABSTRACT: Bladder cancer (BLCA) is a prevalent cancer with high case-fatality rates and a substantial economic burden worldwide. Understanding its molecular underpinnings to guide clinical management is crucial. Ferroptosis, a recently described non-apoptotic form of cell death, is initiated by the lethal accumulation of iron-dependent lipid peroxidation products. Despite growing interest, the roles and vulnerabilities determining ferroptosis sensitivity in BLCA remain unclear. Re-analysis of single-cell RNA data reveals a decrease in high-ferroptosis cancer cells as BLCA advances. USP52/PAN2 is identified as a key regulator of ferroptosis in BLCA through an unbiased siRNA screen targeting 96 deubiquitylases (DUBs). Functionally, USP52 depletion impedes glutathione (GSH) synthesis by promoting xCT p

SUBMITTER: Liu J 

PROVIDER: S-EPMC11615784 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature